Method and system for assessing eye disease

ABSTRACT

Methods and a device comprising a controller/processor unit ( 664 ), a visual test-pattern unit ( 660 ), a competing sensory stimuli generating unit ( 662 ), a user input device ( 666 ), an ouput device ( 668 ) and a storage unit ( 670 ) for detecting eye disease and for assessing the clinical stage of an eye disease in an individual is disclosed. The methods include projecting test patterns onto the retina of a tested eye and subjecting the individual to a competing sensory stimuli. The competing stimuli may be of various different sensory modalities including visual, auditory, or other sensory modalities. If the individual perceives a difference in at least one localized part of the perceived image of a test pattern as compared to a predefined reference pattern, the individual provides a response indicative of the difference or differences. The responses are processed to assess the severity of eye disease if a disease is detected, or to determine the clinical stage of a detected eye disease.

FIELD OF THE INVENTION

This invention generally relates to systems, devices, and methods foradministering eye tests and for detecting, assessing, and classifyingeye disease in patients.

BACKGROUND OF THE INVENTION

Age-related macular degeneration (AMD) is the leading cause of blindnessamong people over the age of 50 in the western world. It is a bilateral,although asymmetric disease, and comes in two forms. Dry ornon-neovascular AMD is the more common and milder form of AMD,accounting for 85-90% of all AMD. The key identifier for dry AMD issmall, round, white-yellow lesions (also known as Drusen) in the macula.Vision loss associated with dry AMD is far less dramatic than in thecase of wet AMD. Recent publications indicate that dietary supplementsincluding antioxidants and minerals reduce the progression of advancedAMD by 25% in patients with intermediate (non-vascular) AMD. It isestimated that as many as 14 million people suffer from dry AMD in theUnited States alone.

Wet AMD is less prevalent than the dry form, accounting for about 10-15%of AMD cases. The term “wet” denotes choroidal neovascularization (CNV),in which abnormal blood vessels develop beneath the retinal pigmentepithelium (RPE) layer of the retina. Wet AMD is characterized by thedevelopment of choroidal angiogenesis which causes severe, andpotentially rapid, visual deterioration. The visual distortion typicallyconsists of perceiving straight lines as curved due to deformation ofthe retina in a region overlying the choroidal angiogenesis. The wetform of AMD accounts for about 60% of all cases of adult blindness inthe United States. In the U.S. alone there are 200,000 new cases of wetAMD every year and a total of 1.7 million blind people from AMD.

Treatment modalities for wet AMD may include laser photocoagulation andPhotodynamic therapy (PDT). Experimental treatments that are undercurrent investigation include feeder vessel coagulation andtrans-pupillary thermotherapy (TTT). All these proven or experimentaltherapies may halt or slow progression of the disease and will usuallynot improve visual function. Therefore, early detection is crucial toprevent severe visual loss.

Since approximately 12% of dry AMD cases develop wet AMD and subsequentblindness within 10 years, a patient diagnosed with dry AMD must beroutinely examined by an ophthalmologist once or twice a year, dependingon the severity of his condition. The patient is usually also given aso-called “Amsler grid” for weekly self-examination at home for symptomsof wet AMD. The patient is advised to consult an ophthalmologistimmediately in the event that symptoms are noticed. The Amsler grid andits modifications (such as the “threshold Amsler” or the “red Amsler”)have been shown to be poor detectors of early changes associated withwet AMD for several reasons. One reason is the phenomenon of“filling-in” whereby the brain fills in missing parts in the pattern orcorrects defects or distortions in the pattern. The subject thus failsto perceive a distorted pattern as being distorted. Another problem withthe Amsler grid is the inability of patients to adequately fixate theirvision on a fixed point while taking the test. The Amsler test alsosuffers from low compliance stemming from the non-interactive nature ofthe test.

The degree of visual deterioration is a function of the size of thelesion and its proximity to the fovea at the time of diagnosis. Althoughmost lesions probably start outside the foveal area, 70% of the lesionsare already foveal and large (>1500 microns) at the time of diagnosis.It is therefore crucial to identify the lesions at the earliest possiblestage, while they are still small and have not reached the fovea. It isknown that 70% of lesions diagnosed as treatable become untreatablewithin less than three months, which indicates that the progression ofthe disease is relatively rapid. As many as 50% of patients with wet AMDare already ineligible for treatment when they first consult theirophthalmologist because the disease has progressed considerably. This isdue to the poor validity of existing self-assessment methods fordetecting an AMD-related lesion at an early stage, and the time lapsedbetween noticing the symptoms and seeing an ophthalmologist.

A reliable method for diagnosing wet AMD at the earliest possible stage,in conjunction with a referral system aimed at lowering the incidence ofvisual deterioration in this devastating disease, are imperative. Ifdetected early, laser therapy to destroy the abnormal blood vessels mayprevent additional vision loss. It is therefore crucial to detect thetransition from dry to wet AMD as early as possible.

Furthermore, there is a long felt need for simple and inexpensivemethods for classifying or assessing the stages of a visual disordersuch as in patients with AMD.

SUMMARY OF THE INVENTION

There is therefore provided in accordance with an embodiment of thepresent invention a method for detecting eye disease in an individual.the method includes the steps of:

-   -   (a) projecting a first pattern on a first location on the retina        of an eye of the individual;    -   (b) fixating the individual's vision on a fixation target        projected on the retina at or about the first location;    -   (c) hiding at least a portion of the first pattern;    -   (d) projecting a second pattern on a second location of the        retina to allow the individual to form a perceived image of the        second pattern;    -   (e) receiving from the individual input indicative of a        difference in at least one localized part of the perceived image        as compared to a predefined reference pattern, if the individual        detected a difference;    -   (f) repeating steps (a) to (e) a number of times to obtain a        plurality of data, wherein in at least some of the repetitions        of steps (a) to (e), the individual is subjected to a competing        sensory stimulus; and    -   (g) processing the plurality of data to determine if the        individual belongs to a group having a defined clinical stage of        an eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a sensory stimuluseffective in modifying the ability of the individual to report adifference in at least one localized part of the perceived image ascompared to a predefined reference pattern when the difference isperceived due to the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, steps (a) to (g) are performed in the order recited above.

Furthermore, in accordance with another embodiment of the presentinvention, the hiding is performed in response to the fixating.

Furthermore, in accordance with another embodiment of the presentinvention, the eye disease is selected from the group consisting ofage-related macular degeneration, choroidal neovascularization, ocularhystoplasmosis, myopia, central serous retinopathy, central serouschoroidopathy, glaucoma, diabetic retinopathy, media opacities,cataract, retinitis pigmentosa, optic neuritis, epiretinal membrane,vascular abnormalities, vascular occlusions, choroidal dystrophies,retinal dystrophies, macular hole, choroidal degeneration, retinaldegeneration, lens abnormalities, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, steps (a) to (e) are repeated while changing the position ofat least one of the first pattern and the second pattern to map aselected region of the retina at a desired resolution.

Furthermore, in accordance with another embodiment of the presentinvention, steps (a) to (e) are repeated while changing the orientationof the first pattern and of the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, competing stimulus is selected from a competing stimuluspresented before the projecting of the second pattern, a competingstimulus presented during at least part of the duration of projecting ofthe second pattern, a competing stimulus presented after the projectingof the second pattern and a competing stimulus which temporally overlapsat least a part of the duration of the projecting of the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is selected from a fixed stimulus, avarying stimulus and a transient stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is selected from a stimulus which doesnot vary for the duration of presentation of the second pattern and astimulus which varies within the duration of presentation of the secondpattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is selected from a visualstimulus, an auditory stimulus, a somatosensory stimulus, a tactilestimulus, and a nociceptive stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a distracting sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a visual stimulus which isnot a part of the first pattern or of the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is an auditory stimulusselected from a single frequency sound and a multi-frequency sound.

Furthermore, in accordance with another embodiment of the presentinvention, at least one parameter of the competing sensory stimulus ismodified in one or more of the repetitions of steps (a) to (e).

Furthermore, in accordance with another embodiment of the presentinvention, the at least one parameter is selected from the duration ofthe competing stimulus, the time of initiating the presenting of thecompeting sensory stimulus relative to the time of projecting of thesecond pattern, one or more characteristics of the competing sensorystimulus, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is an auditory stimulus, andthe at least one parameter of said auditory stimulus which is modifiedis selected from the intensity of the auditory stimulus, the waveform ofthe auditory stimulus, the frequency of the auditory stimulus, thefrequency distribution of the auditory stimulus, the frequency contentof the auditory stimulus, the duration of the auditory stimulus, theenvelope of the auditory stimulus and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a visual stimulus and theat least one parameter of said competing stimulus which is modified isselected from the size of the stimulus, the shape of the stimulus, thepattern of the stimulus, the duration of presentation of the stimulus,the color of the stimulus, the intensity of the stimulus, the luminanceof the stimulus, the chrominance of the stimulus, the temporal variationof the stimulus, the timing of presentation of the stimulus to theindividual, the position of projecting the stimulus on the retina, theposition of the stimulus on said retina, the rate of movement of saidstimulus on said retina, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a visual stimulus selected from avisual stimulus which is a part of the second pattern and a visualstimulus which is not a part of the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a noisy visual background projectedon the retina.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is selected from a stimulus which doesnot vary for the duration of presentation of the second pattern and astimulus which varies within the duration of presentation of the secondpattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus comprises an artificialdistortion introduced into the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion introduced into the second patternmimics the appearance of the distortion perceived by an individual whena test pattern identical to the reference pattern is projected at alocation of the retina of the individual which comprises a retinal orchoroidal abnormality or a retinal and a choroidal abnormality.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion comprises at least a portion of thesecond pattern which is perceivably different than the correspondingpart of the reference pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion is selected from at least oneportion of the second pattern which is distorted or shifted incomparison with the reference pattern, at least one optical property ofat least one part of the second pattern which is different than thecorresponding optical property of the remaining part of the secondpattern, at least one portion of the second pattern which is visiblydifferent in comparison with the corresponding portion of the referencepattern, at least one portion of the second pattern is missing incomparison with said reference pattern, and at least one portion of thesecond pattern which is blurred in comparison with the remaining part ofthe second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is selected from a fixedvisual stimulus, a time varying visual stimulus, and a transient visualstimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the first pattern, the reference pattern, and the secondpattern are selected from a straight line and a segmented straight line.

Furthermore, in accordance with another embodiment of the presentinvention, the plurality of data of step (e) includes for eachrepetition of steps (a) to (e) one or more data items selected from thegroup consisting of data representing the position on the retina of thesecond pattern, data representing the orientation of the second pattern,data representing the position within the second pattern of the at leastone localized part of the difference, and data representing one or morecharacteristics of the competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a visual competing stimulusincluded in the second pattern and the plurality of data furtherincludes data representing the position of the visual competing stimuluswithin the second pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the step of processing includes determining for at least onegroup of competing sensory stimuli having common stimulus parameters thevalue of a competition grade and determining if the individual belongsto a group having a specific clinical stage of the eye disease based onthe determined value of the competition grade.

Furthermore, in accordance with another embodiment of the presentinvention, the competition grade represents the efficiency of a group ofcompeting sensory stimuli having common stimulus parameters inpreventing the tested individual from reporting the presence of thedifference of the perceived image, when said difference is caused by theeye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the value of the competition grade is computed as thepercentage of projected second patterns for which the individualreported at least one localized difference, caused by the eye disease,between the perceived image of the second pattern and the referencepattern, out of the total number of projected second patterns for whichthe individual was subjected to competing sensory stimuli belonging to agroup of competing sensory stimuli having common stimulus parameters.

Furthermore, in accordance with another embodiment of the presentinvention, the second pattern is a segmented straight line, thecompeting sensory stimulus includes one or more segments of thesegmented line which are shifted relative to the remaining segments ofthe straight line to form an artificial distortion having a definedamplitude. The position of the artificial distortion along the segmentedstraight line varies in at least some repetitions of the projecting ofthe second pattern, and within each group of competing sensory stimulihaving common stimulus parameters, the amplitude of the artificialdistortion is the same.

Furthermore, in accordance with another embodiment of the presentinvention, the second pattern is a segmented straight line, saidcompeting sensory stimulus comprises one or more segments of saidsegmented line which are shifted relative to the remaining segments ofsaid straight line to form an artificial distortion having a definedamplitude, and wherein said at least one localized difference isdetermined to be caused by said eye disease if the computed distancebetween the center of said artificial distortion and the position alongthe length of said segmented line at which said individual reported saidat least one localized difference exceeds a preset value.

There is further provided, in accordance with a embodiment of thepresent invention, a method for obtaining data useful for detecting eyedisease in an individual, the method includes the steps of:

-   (a) projecting a first pattern on a first location on the retina of    an eye of the individual;-   (b) fixating the individual's vision on a fixation target projected    on the retina at or about the first location;-   (c) hiding at least a portion of the first pattern;-   (d) projecting a second pattern on a second location of the retina    to allow the individual to form a perceived image of the second    pattern;-   (e) receiving from the individual input indicative of a difference    in at least one localized part of the perceived image as compared to    a predefined reference pattern, if the individual detected such a    difference; and-   (f) repeating steps (a) to (e) a number of times, wherein for at    least some of the repetitions of steps (a) to (e), the individual is    subjected to a competing sensory stimulus to obtain a plurality of    data useful for detecting eye disease in the individual.

There is further provided, in accordance with a embodiment of thepresent invention, a method for detecting eye disease in an individual.The method includes the steps of:

-   -   fixating the individual's vision at or about a fixation target        projected at a first retinal location of the retina of an eye of        the individual;    -   projecting for a first duration a test pattern at a second        retinal location of the eye, to allow the individual to form a        perceived image of the test pattern;    -   receiving from the individual input indicative of a difference        in at least one localized part of the perceived image as        compared to a predefined reference pattern, if the individual        detected such a difference;    -   repeating the steps of fixating, projecting and receiving a        number of times to obtain a plurality of data, wherein in at        least some of the repetitions of the steps of fixating,        projecting, and receiving, the individual is subjected for a        second duration to a competing sensory stimulus; and    -   processing the plurality of data to determine if the individual        belongs to a group having a defined clinical stage of the eye        disease.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a sensory stimuluseffective in modifying the ability of the individual to report adifference in at least one localized part of the perceived image ascompared to a predefined reference pattern when the difference isperceived due to the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the first duration is in the range of 10 milliseconds to 20seconds.

Furthermore, in accordance with another embodiment of the presentinvention, the first duration is in the range of 100-160 milliseconds.

Furthermore, in accordance with another embodiment of the presentinvention, the step of fixating, the step of projecting, the step ofreceiving, the step of repeating and the step of analyzing are performedin the order recited above.

Furthermore, in accordance with another embodiment of the presentinvention, the projecting is performed in response to the fixating.

Furthermore, in accordance with another embodiment of the presentinvention, the eye disease is selected from the group consisting ofage-related macular degeneration, choroidal neovascularization, ocularhystoplasmosis, myopia, central serous retinopathy, central serouschoroidopathy, glaucoma, diabetic retinopathy, media opacities,cataract, retinitis pigmentosa, optic neuritis, epiretinal membrane,vascular abnormalities, vascular occlusions, choroidal dystrophies,retinal dystrophies, macular hole, choroidal degeneration, retinaldegeneration, lens abnormalities, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, in at least some of the repetitions of the steps of fixating,projecting, and receiving, the position of projecting of the testpattern on the retina is changed to map a selected region of the retinaat a desired resolution.

Furthermore, in accordance with another embodiment of the presentinvention, in at least some of the repetitions of the steps of fixating,projecting, and receiving, the orientation of projecting of the testpattern on the retina is changed.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is selected from a competingstimulus presented before the projecting of the test pattern, acompeting stimulus presented during at least part of the duration ofprojecting of the test pattern, a competing stimulus presented after theprojecting of the test pattern, and a competing stimulus whichtemporally overlaps at least a part of the duration the projecting ofthe test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is selected from a fixed stimulus, avarying stimulus and a transient stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is selected from a stimulus which doesnot vary for the duration of presentation of the test pattern and astimulus which varies within the duration of presentation of the testpattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is selected from a visualstimulus, an auditory stimulus, a somatosensory stimulus, a tactilestimulus, and a nociceptive stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a distracting sensorystimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a visual stimulus which isnot a part of the test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is an auditory stimulusselected from a single frequency sound and a multi-frequency sound.

Furthermore, in accordance with another embodiment of the presentinvention, at least one parameter of the competing sensory stimulus ismodified in one or more of the repetitions of the steps of fixating,projecting, and receiving.

Furthermore, in accordance with another embodiment of the presentinvention, the at least one parameter which is modified is selected fromthe duration of the competing stimulus, the time of initiating thepresenting of the competing sensory stimulus relative to the time ofprojecting of the test pattern, one or more characteristics of thecompeting sensory stimulus, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is an auditory stimulus. Theat least one parameter of the auditory stimulus which is modified isselected from the intensity of the auditory stimulus, the waveform ofthe auditory stimulus, the frequency of the auditory stimulus, thefrequency distribution of the auditory stimulus, the frequency contentof the auditory stimulus, the duration of the auditory stimulus, theenvelope of the auditory stimulus and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is a visual stimulus and theat least one parameter of the competing stimulus which is modified isselected from the size of the stimulus, the shape of the stimulus, thepattern of the stimulus, the duration of presentation of the stimulus,the color of the stimulus, the intensity of the stimulus, the luminanceof the stimulus, the chrominance of the stimulus, the temporal variationof the stimulus, the timing of presentation of the stimulus to theindividual, the position of projecting the stimulus on the retina, therate of movement of the stimulus on the retina, and combinationsthereof.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a visual stimulus selected from avisual stimulus which is a part of the test pattern and a visualstimulus which is not a part of the test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a noisy visual background projectedon the retina.

Furthermore, in accordance with another embodiment of the presentinvention, the sensory stimulus is selected from a stimulus which doesnot vary for the duration of presentation of the test pattern and astimulus which varies within the duration of presentation of the testpattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus includes an artificialdistortion introduced into the test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion introduced into the test patternmimics the appearance of the distortion perceived by an individual whena test pattern identical to the reference pattern is projected at alocation of the retina of the individual which includes a retinalabnormality, or a choroidal abnormality, or a retinal and a choroidalabnormality.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion comprises at least a portion of thetest pattern which is perceivably different than the corresponding partof the reference pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the artificial distortion is selected from at least oneportion of the test pattern being distorted or shifted in comparisonwith the reference pattern, at least one optical property of at leastone part of the test pattern being different than the correspondingoptical property of the remaining part of the test pattern, at least oneportion of the test pattern is visibly different in comparison with thecorresponding portion of the reference pattern, at least one portion ofthe test pattern is missing in comparison with the reference pattern,and at least one portion of the test pattern being blurred in comparisonwith the remaining part of the test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimulus is selected from a fixedvisual stimulus, a time varying visual stimulus, and a transient visualstimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the test pattern, and the reference pattern is selected froma straight line and a segmented straight line.

Furthermore, in accordance with another embodiment of the presentinvention, the plurality of data of the step of repeating includes, foreach repetition of the steps of fixating, projecting and receiving, oneor more data items selected from the group consisting of, datarepresenting the position on the retina of the test pattern, datarepresenting the orientation of the test pattern, data representing theposition within the test pattern of the at least one localized part ofthe difference, and data representing one or more characteristics of thecompeting sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the competing stimulus is a visual competing stimulusincluded in the test pattern and the plurality of data further includesdata representing the position of the visual competing stimulus withinthe test pattern.

Furthermore, in accordance with another embodiment of the presentinvention, the step of processing includes determining for at least onegroup of competing sensory stimuli having common stimulus parameters thevalue of a competition grade, and determining if the individual belongsto a group having a specific clinical stage of the disease based on thedetermined value of the competition grade.

Furthermore, in accordance with another embodiment of the presentinvention, the wherein said competition grade represents the efficiencyof a group of competing sensory stimuli having common stimulusparameters in preventing the tested individual from reporting thepresence of said difference of said perceived image, when saiddifference is caused by said eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the value of the competition grade is computed as thepercentage of projected test patterns for which the individual reportedat least one localized difference determined to be caused by said eyedisease between the perceived image of the test pattern and thereference pattern, out of the total number of projected test patternsfor which the individual was subjected to competing sensory stimulibelonging to a group of competing sensory stimuli having common stimulusparameters.

Furthermore, in accordance with another embodiment of the presentinvention, the test pattern is a segmented straight line, the competingsensory stimulus includes one or more segments of the segmented linewhich are shifted relative to the remaining segments of the straightline to form an artificial distortion having a defined amplitude. Theposition of the artificial distortion along the segmented straight linevaries in at least some repetitions of the projecting of the testpattern, and within each group of competing sensory stimuli havingcommon stimulus parameters, the amplitude of the artificial distortionis the same.

Furthermore, in accordance with another embodiment of the presentinvention, the test pattern is a segmented straight line, the competingsensory stimulus comprises one or more segments of the segmented linewhich are shifted relative to the remaining segments of the straightline to form an artificial distortion having a defined amplitude. The atleast one localized difference is determined to be caused by the eyedisease if the computed distance between the center of the artificialdistortion and the position along the length of the segmented line atwhich the individual reported the at least one localized differenceexceeds a preset value.

Furthermore, in accordance with another embodiment of the presentinvention, the relationship of the first duration and the secondduration is selected from, the first duration is identical to the secondduration, the second duration precedes the first duration, and the firstduration at least partially overlaps with the second duration.

There is also provided, in accordance with an embodiment of the presentinvention, a method for obtaining data useful for detecting eye diseasein an individual. The method includes the steps of:

-   -   fixating the individual's vision at or about a fixation target        projected at a first retinal location of the retina of an eye of        the individual;    -   projecting for a first duration a test pattern at a second        retinal location of the eye, to allow the individual to form a        perceived image of the test pattern;    -   receiving from the individual input indicative of a difference        in at least one localized part of the perceived image as        compared to a predefined reference pattern, if the individual        detected such a difference; and    -   repeating the steps of fixating, projecting and receiving a        number of times, such that for at least some of the repetitions        of the steps of fixating, projecting, and receiving, the        individual is subjected for a second duration to a competing        sensory stimulus, to obtain a plurality of data useful for        detecting eye disease in the individual.

There is also provided, in accordance with an embodiment of the presentinvention, a system for detecting eye disease in an individual, thesystem includes:

-   -   means for projecting patterns on the retina of an eye of the        individual;    -   means for fixating the individual's vision on a fixation target        projected on the retina;    -   means for providing input representative of the position of a        selected region of the retina at which a difference is observed        by the individual between a perceived image of one of the        patterns and a predetermined reference pattern;    -   means for controllably delivering to the individual competing        sensory stimuli; and    -   processing means operatively coupled to the means for        projecting, the means for fixating, the means for providing        input and the means for controllably delivering competing        sensory stimuli. The processing means is configured to perform        the steps of,    -   (a) projecting a first pattern at a first location on the        retina,    -   (b) determining when the individual's vision is fixated on the        fixation target,    -   (c) hiding at least a portion of the first pattern after the        individual's vision is fixated on the fixation target,    -   (d) projecting a second pattern at a second location on the        retina to allow the individual to form a perceived image of the        second pattern, and    -   (e) receiving from the individual input indicative of a        difference in at least one localized part of the perceived image        as compared to a predefined reference pattern, if the individual        detected such a difference;    -   (f) repeating steps (a) to (e) a number of times to obtain a        plurality of data, wherein in at least some of the repetitions        of steps (a) to (e), the individual is subjected to a competing        sensory stimulus.        Furthermore, in accordance with another embodiment of the        present invention, the system further includes means for storing        the plurality of data.

Furthermore, in accordance with another embodiment of the presentinvention, the means for controllably delivering to the individualcompeting sensory stimuli are selected from means for delivering visualstimuli, means for delivering auditory stimuli, means for deliveringsomatosensory stimuli, means for delivering tactile stimuli, and meansfor delivering nociceptive stimuli.

Furthermore, in accordance with another embodiment of the presentinvention, the processing means includes at least one processing unitselected from a processor, a microprocessor, a computer, a personalcomputer, a laptop computer, a controller, a remote processor orcomputer, a server, a remote server, a networked computer, andcombinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the means for projecting is selected from a display device, abeam scanning device, and a laser scanning ophtalmoscope-like device.

Furthermore, in accordance with another embodiment of the presentinvention, at least one of the means for fixating and means forproviding input comprises a device selected from the group consisting ofa pointing device, a computer input device, a keyboard, a mouse, a lightpen, a touch sensitive display device, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the means for projecting patterns is configured forprojecting test patterns and fixation targets on the retina.

Furthermore, in accordance with another embodiment of the presentinvention, at least one of the means for projecting, the means forproviding input and the means for fixating includes one or more devicesselected from a touch sensitive display device, a pointing device, alight pen, joystick, a mouse, a keyboard, a computer input device, andcombinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the means for projecting, the means for fixating and themeans for providing input comprise a touch-sensitive display device.

Furthermore, in accordance with another embodiment of the presentinvention, the means for fixating comprises a device for moving a cursoror a pattern projected by the means for projecting.

Furthermore, in accordance with another embodiment of the presentinvention, the means for fixating is selected from a pointing device, acomputer input device, a computer mouse, a keyboard, a joystick, a lightpen and a touch sensitive screen.

Furthermore, in accordance with another embodiment of the presentinvention, the means for providing input comprises a pointing device foroperatively moving a cursor or a pattern projected by the means forprojecting.

Furthermore, in accordance with another embodiment of the presentinvention, the processing means are configured to perform the step ofprocessing the plurality of data to determine if the individual belongsto a group having a defined clinical stage of the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes communication means forcommunicating the plurality of data for processing outside of thesystem.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes communication means forcommunicating with one or more devices outside of the system.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimuli include visual competingstimuli and the means for controllably delivering to the individualcompeting sensory stimuli includes means for controllably modifying thepatterns projected on the retina.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes means for providing output to auser. The means for providing output is operatively coupled to theprocessing means.

There is also provided, in accordance with an embodiment of the presentinvention, a system for detecting eye disease in an individual. Thesystem includes:

-   -   a projecting unit for projecting test patterns and fixation        targets on the retina of an eye of the individual;    -   at least one input device for providing input representing a        difference observed by the individual between a perceived image        of one of the test patterns and a predetermined reference        pattern;    -   a competing sensory stimuli generating unit for controllably        subjecting the individual to competing sensory stimuli; and    -   at least one processing unit operatively coupled to the        projecting unit, the at least one input device, and the        competing sensory stimuli generating unit. The at least one        processing unit is configured to perform the steps of,    -   (a) projecting a first pattern at a first location on the        retina,    -   (b) determining when the individual's vision is fixated on the        fixation target,    -   (c) hiding at least a portion of the first pattern after the        individual's vision is fixated on the fixation target,    -   (d) projecting a second pattern at a second location on the        retina to allow the individual to form a perceived image of the        second pattern,    -   (e) receiving from the individual input indicative of a        difference in at least one localized part of the perceived image        as compared to a predefined reference pattern, if the individual        detected such a difference, and    -   (f) repeating steps (a) to (e) a number of times to obtain a        plurality of data, wherein in at least some of the repetitions        of steps (a) to (e), the competing sensory stimuli generating        unit subjects the individual to a competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes a storage device for storing theplurality of data.

Furthermore, in accordance with another embodiment of the presentinvention, the projecting unit comprises the competing sensory stimuligenerating unit.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimuli generating unit is selectedfrom a unit for delivering visual stimuli, a unit for deliveringauditory stimuli, a unit for delivering somatosensory stimuli, a unitfor delivering tactile stimuli, and a unit for delivering nociceptivestimuli.

Furthermore, in accordance with another embodiment of the presentinvention, the data is selected from, the presence of the differencewithin the perceived image of the second pattern, the approximateposition within the perceived image of the difference, the position of asecond pattern relative to the fixation target, the orientation of thesecond pattern on the retina, the presence of a distortion in the secondpatterns, the position of the distortion within the second pattern, thepresence of a visually perceivable difference between one or more partsof the perceived image of the second pattern and the predefinedreference pattern, the position of the one or more parts within theperceived image, one or more characteristics of the competing sensorystimuli, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the at least one processing unit is selected from aprocessor, a microprocessor, a computer, a personal computer, a laptopcomputer, a controller, a remote processor or computer, a server, aremote server, a networked computer, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the projecting unit is selected from a display device, a beamscanning device, and a laser scanning ophtalmoscope-like device.

Furthermore, in accordance with another embodiment of the presentinvention, the display device comprises a touch sensitive displaydevice.

Furthermore, in accordance with another embodiment of the presentinvention, the at least one input device includes a device selected fromthe group consisting of a pointing device, a computer input device, akeyboard, a mouse, a light pen, a touch sensitive display device, andcombinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, at least one of the projecting unit and the input deviceincludes one or more devices selected from a touch sensitive displaydevice, a pointing device, a light pen, joystick, a mouse, a keyboard, acomputer input device, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes communication means forcommunicating with one or more devices outside of the system.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes at least one output deviceoperatively coupled to the at least one processing unit for providingoutput to a user.

There is also provided, in accordance with another embodiment of thepresent invention, a system for detecting eye disease in an individual.The system includes:

-   -   means for projecting test patterns and fixation targets on the        retina of an eye of the individual;    -   means for fixating the individual's vision on a fixation target        projected on the retina;    -   means for providing input representative of the position on the        retina at which a difference is observed by the individual        between a perceived image of one of the patterns and a        predetermined reference pattern;    -   means for controllably delivering to the individual competing        sensory stimuli; and    -   processing means operatively coupled to the means for        projecting, the means for fixating, the means for providing        input, and the means for controllably delivering to said        individual competing sensory stimuli. The processing means is        configured to perform the steps of fixating the individual's        vision at or about a fixation target projected at a first        location of the retina, projecting for a selected duration a        test pattern at a second location of the retina to allow the        individual to form a perceived image of the test pattern,        receiving from the individual input indicative of a difference        in at least one localized part of the perceived image of the        step of projecting as compared to a predefined reference        pattern, if the individual detected such a difference, and        repeating the steps of fixating, projecting and receiving a        number of times to obtain a plurality of data, wherein in at        least some of the repetitions of the steps of fixating,        projecting and receiving, the individual is subjected to a        competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the processing means is configured for performing the step ofanalyzing the plurality of data to determine whether the individual hasan eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes means for storing the plurality ofdata.

Furthermore, in accordance with another embodiment of the presentinvention, the means for controllably delivering to the individualcompeting sensory stimuli are selected from means for delivering visualstimuli, means for delivering auditory stimulus, means for deliveringsomatosensory stimuli, means for delivering tactile stimuli, and meansfor delivering nociceptive stimuli.

Furthermore, in accordance with another embodiment of the presentinvention, the processing means includes at least one processing unitselected from a processor, a microprocessor, a computer, a personalcomputer, a minicomputer, a laptop computer, a controller, a remoteprocessor or computer, a server, a remote server, a networked computer,and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the means for projecting is selected from a display device, abeam scanning device, and a laser scanning ophtalmoscope-like device.

Furthermore, in accordance with another embodiment of the presentinvention, at least one of the means for fixating and means forproviding input includes a device selected from the group consisting ofa pointing device, a computer input device, a keyboard, a mouse, agraphic tablet, a light pen, a touch sensitive screen, and combinationsthereof.

Furthermore, in accordance with another embodiment of the presentinvention, the means for fixating includes a device for moving a cursoror a pattern projected by the means for projecting.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes communication means forcommunicating with one or more devices outside of the system.

Furthermore, in accordance with another embodiment of the presentinvention, the means for providing input includes a pointing device foroperatively moving a cursor or a pattern projected by the means forprojecting.

Furthermore, in accordance with another embodiment of the presentinvention, the processing means are configured to perform the step ofprocessing the plurality of data to determine if the individual belongsto a group having a defined clinical stage of the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the competing sensory stimuli comprise visual competingstimuli and the means for controllably delivering to said individualcompeting sensory stimuli comprise means for controllably modifying testpatterns projected on the retina.

Furthermore, in accordance with another embodiment of the presentinvention, the system also comprises means for providing output to auser. The means for providing output is operatively coupled to theprocessing means.

There is also provided, in accordance with another embodiment of thepresent invention, a system for detecting eye disease in an individual.The system includes:

-   -   a projecting unit for projecting test patterns and fixation        targets on the retina of an eye of the individual;    -   at least one input device for providing input representing a        difference observed by the individual between a perceived image        of one of the test patterns and a predetermined reference        pattern;    -   a competing sensory stimuli generating unit for controllably        subjecting the individual to competing sensory stimuli; and    -   at least one processing unit operatively coupled to the        projecting unit, the at least one input device, and the        competing sensory stimuli generating unit. The at least one        processing unit is configured to perform the steps of,        -   fixating the individual's vision at or about a fixation            target projected at a first location of the retina,        -   projecting for a selected duration a test pattern at a            second location of the retina, to allow the individual to            form a perceived image of the test pattern,        -   receiving from the individual input indicative of a            difference in at least one localized part of the perceived            image of the step of projecting as compared to a predefined            reference pattern, if the individual detected such a            difference, and        -   repeating the steps of fixating, projecting and receiving a            number of times to obtain a plurality of data, wherein in at            least some of the repetitions of the steps of fixating,            projecting and receiving, the individual is subjected to a            competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the system further includes a storage device for storing theplurality of data.

Furthermore, in accordance with another embodiment of the presentinvention, the projecting unit comprises said competing sensory stimuligenerating unit.

Furthermore, in accordance with another embodiment of the presentinvention, the data is selected from, the presence of the differencewithin the perceived image, the approximate position within theperceived image of the difference, the position of the test patternsrelative to the fixation target, the orientation of the test patterns onthe retina, the presence of a distortion in the test patterns, theposition of the distortion within a test pattern, the presence of avisually perceivable difference between one or more parts of theperceived image and the predefined reference pattern, the position ofthe one or more parts within the perceived image, one or morecharacteristics of the competing sensory stimuli, and combinationsthereof.

Furthermore, in accordance with another embodiment of the presentinvention, the processing unit is selected from a processor, amicroprocessor, a computer, a personal computer, a laptop computer, acontroller, a remote processor or computer, a server, a remote server, anetworked computer, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the projecting unit is selected from a display device, a beamscanning device, and a laser scanning ophtalmoscope-like device.

Furthermore, in accordance with another embodiment of the presentinvention, the display device comprises a touch sensitive displaydevice.

Furthermore, in accordance with another embodiment of the presentinvention, the at least one input device comprises a device selectedfrom the group consisting of a pointing device, a computer input device,a keyboard, a mouse, a light pen, a touch sensitive display device, andcombinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, at least one of the projecting unit and the input devicecomprises one or more devices selected from a touch sensitive displaydevice, a pointing device, a light pen, joystick, a mouse, a keyboard, acomputer input device, and combinations thereof.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes communication means forcommunicating with one or more devices outside of the system.

Furthermore, in accordance with another embodiment of the presentinvention, the system also includes at least one output deviceoperatively coupled to the at least one processing unit for providingoutput to a user.

There is also provided, in accordance with another embodiment of thepresent invention, a program storage device readable by machine,tangibly embodying a program of instructions executable by the machineto perform method steps for detecting eye disease in an individual. Theprogram includes the steps of:

-   -   (a) projecting a first pattern on a first location on the retina        of an eye of the individual;    -   (b) fixating the individual's vision on a fixation target        projected on the retina at or about the first location;    -   (c) hiding at least a portion of the first pattern;    -   (d) projecting a second pattern on a second location of the        retina to allow the individual to form a perceived image of the        second pattern;    -   (e) receiving from the individual input indicative of a        difference in at least one localized part of the perceived image        as compared to a predefined reference pattern, if the individual        detected such a difference; and    -   (f) repeating steps (a) to (e) a number of times to obtain a        plurality of data, wherein in at least some of the repetitions        of steps (a) to (e), the individual is subjected to a competing        sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the repeating of step (f) is performed such that in at leastsome of the repetitions of steps (a) to (e) the location of projectingof at least the second pattern on the retina is changed.

Furthermore, in accordance with another embodiment of the presentinvention, the method steps of the program also include the step ofprocessing the plurality of data to determine if the individual belongsto a group having a defined clinical stage of the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the method steps of the program also include the step ofcommunicating the plurality of data to a device external to the computerfor processing the plurality of data to determine if the individualbelongs to a group having a defined clinical stage of the eye disease.

There is also provided, in accordance with another embodiment of thepresent invention, a computer program product comprising a computeruseable medium having computer readable program code embodied thereinfor detecting eye disease in an individual. The computer program productincludes:

-   -   computer readable program code for causing a computer or a        projecting device operatively coupled to the computer to project        a first pattern on a first location on the retina of an eye of        the individual;    -   computer readable program code for causing the computer to        determine when the individual's vision is fixated on a fixation        target projected on the retina at or about the first location        and for hiding at least a portion of the first pattern when the        individual's vision is fixated on the fixation target;    -   computer readable program code for causing the computer to        project a second pattern at a second location of the retina to        allow the individual to form a perceived image of the second        pattern;    -   computer readable program code for causing the computer to        receive from said individual input indicative of a difference in        at least one localized part of the perceived image as compared        to a predefined reference pattern, if the individual detected        such a difference; and    -   computer readable program code for causing the computer to        perform a selected number of repetitions of the projecting of a        first pattern, the determining when the individual's vision is        fixated on the fixation target projected on the retina, the        hiding of at least a portion of the first pattern when the        individual's vision is fixated on the fixation target, the        projecting of a second pattern at a second location of the        retina to allow the individual to form a perceived image of the        second pattern, and the receiving from the individual of input        indicative of a difference in at least one localized part of the        perceived image as compared to the predefined reference pattern        if the individual detected such a difference, for obtaining a        plurality of data, wherein in at least some of the repetitions        the individual is subjected to a competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the computer readable program code further includes computerreadable program code for causing the computer to process the pluralityof data to determine whether the individual has an eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the computer readable program code further includes computerreadable program code for causing the computer to communicate theplurality of data to a device external to the computer for processingthe plurality of data to detect the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the computer readable program code further includes computerreadable program code for causing the computer to change the location ofprojecting of at least the second pattern on the retina in at least someof the repetitions.

There is also provided, in accordance with another embodiment of thepresent invention, a program storage device readable by machine,tangibly embodying a program of instructions executable by the machineto perform method steps for detecting eye disease in an individual. Themethod includes the steps of:

-   -   fixating the individual's vision at or about a fixation target        projected at a first retinal location of the retina of an eye of        the individual;    -   projecting for a first duration a test pattern at a second        retinal location of the eye, to allow the individual to form a        perceived image of the test pattern;    -   receiving from the individual input indicative of a difference        in at least one localized part of the perceived image as        compared to a predefined reference pattern, if the individual        detected such a difference; and    -   repeating the steps of fixating, projecting and receiving a        number of times to obtain a plurality of data, wherein for at        least some of the repetitions of the steps of fixating,        projecting, and receiving, the individual is subjected for a        second duration to a competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, in at least some of the repetitions of the step of repeating,the location of projecting of the test pattern on the retina is changed.

Furthermore, in accordance with another embodiment of the presentinvention, the method steps of the program also include the step ofprocessing the plurality of data to determine if the individual belongsto a group having a defined clinical stage of the eye disease.

Furthermore, in accordance with another embodiment of the presentinvention, the method steps of the program also include the step ofcommunicating the plurality of data to a device external to the computerfor processing the plurality of data to determine if the individualbelongs to a group having a defined clinical stage of the eye disease.

There is also provided, in accordance with another embodiment of thepresent invention, a computer program product comprising a computeruseable medium having computer readable program code embodied thereinfor detecting eye disease in an individual. The computer program productincludes:

-   -   computer readable program code for causing a computer or a        projecting device operatively coupled to the computer to project        a fixation target at a first retinal position of an eye of the        individual;    -   computer readable program code for causing the computer to        determine when the individual's vision is fixated at or about        the fixation target, and for projecting for a selected duration,        when the individual's vision is fixated on the fixation target,        a test pattern at a second retinal position of the eye, to allow        the individual to form a perceived image of the test pattern;    -   computer readable program code for causing the computer to        receive from the individual input indicative of a difference in        at least one localized part of the perceived image as compared        to a predefined reference pattern, if the individual detected        such a difference; and    -   computer readable program code for causing the computer to        perform a selected number of repetitions of the projecting of        the test pattern, the determining when the individual's vision        is fixated at or about the fixation target, the projecting of a        test pattern at the second location, and the receiving of the        input from the individual if the individual detected such a        difference, for obtaining a plurality of data, wherein in at        least some of the repetitions the individual is subjected to a        competing sensory stimulus.

Furthermore, in accordance with another embodiment of the presentinvention, the computer readable program code further includes computerreadable program code for causing the computer to change the location ofprojecting of the test pattern on the retina in at least some of therepetitions.

Furthermore, in accordance with another embodiment of the presentinvention, the computer readable program code further includes computerreadable program code for causing the computer to process the pluralityof data to determine whether the individual has an eye disease.

Finally, in accordance with another embodiment of the present invention,the computer readable program code also includes computer readableprogram code for causing the computer to communicate the plurality ofdata to a device external to the computer for processing the pluralityof data to detect the eye disease.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings, in which like components aredesignated by like reference numerals, wherein:

FIG. 1 is a schematic diagram illustrating a system for carrying out aneye test to detect an eye disease according to one embodiment of theinvention;

FIG. 2 is a schematic flow chart diagram illustrating a method ofexecuting an eye test for detecting an eye disease using a system suchas the system illustrated in FIG. 1, in accordance with an embodiment ofthe present invention;

FIG. 3 schematically illustrates selected exemplary screenrepresentations including exemplary test patterns which may be presentedto a tested subject, in an exemplary embodiment of the testing method ofthe present invention, and selected schematic representations of how thetest patterns may be perceived by a tested subject in selected stages ofthe testing;

FIGS. 4A-4B are schematic diagrams illustrating some exemplary types ofline series which may be useful for mapping retinal and/or choroidallesions in accordance with some exemplary embodiments of the presentinvention;

FIGS. 5A-5J are schematic diagrams illustrating patterns displayed atvarious different exemplary steps of another embodiment of an eye testperformed by the system illustrated in FIG. 1, and the possibleappearance of the test patterns as they may be perceived by the testsubject at some exemplary steps of the eye test;

FIG. 6 is a schematic diagram useful in understanding an exemplarypositioning accuracy criterion which may be used in the eye testingmethod, in accordance with one exemplary embodiment of the presentinvention;

FIGS. 7A and 7B are schematic diagrams useful in understanding exemplaryproximity criteria which may be used in exemplary embodiments of thepresent invention;

FIG. 8 is a schematic flow diagram useful in understanding a method forperforming a test session and analyzing the results of the test session,in accordance with one possible embodiment of the present invention;

FIG. 9 is a bar graph representing experimental results comparing theperformance of the standard Amsler grid test with the performance of theeye test of the present invention;

FIG. 10 is a schematic diagram illustrating a system including ascanning laser device or another eye scanning device usable for carryingout an eye test according to another preferred embodiment of theinvention;

FIG. 11 is a diagram schematically illustrating four different possibleresponse types of the same patient when the patient is presented with atest pattern including an artificial distortion, such that part of theprojected image of the test pattern falls on a retinal or choroidallesion in the patient's retina;

FIG. 12 is a schematic diagram illustrating in detail part of aschematic artificially distorted test pattern used in the competitionexperiments performed in accordance with an embodiment of the presentinvention;

FIGS. 13 and 14 are schematic diagrams illustrating in detail thecriterion for determining if a position marked by the patient is due toa pathology related observed distortion (PROD) indicating the presenceof a retinal or choroidal lesion or due to an artificially inducedobserved distortion (AIOD) indicating the observation of an artificialdistortion, in accordance with one embodiment of the present invention;

FIG. 15 is a schematic diagram illustrating is a schematic diagramillustrating a system for carrying out an eye test to detect and orassess an eye disease using auditory competing stimuli in accordancewith another embodiment of the present invention;

FIG. 16 is a schematic block diagram illustrating a system for applyingvisual tests and competing sensory stimuli to a test subject, inaccordance with an embodiment of the present invention; and

FIGS. 17A-17J are schematic diagrams illustrating exemplary forms ofvarious different test patterns and competing visual stimuli which maybe used in accordance with some embodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The following terms are used throughout the application: Term DefinitionAD Artificial distortion AIOD Artificially induced observed distortionAMD Age-related macular degeneration CNV Choroidal Neovascularization CSCompeting stimulus DVS Distracting visual stimulus GA Geographic atrophyHRC High risk characteristics LAN Local area network MCPT Macularcomputerized psychophysical test PAN Private area network PDTPhotodynamic Therapy PROD Pathology related observed distortion PSTNPublic service telephone network RPE Retinal pigment epithelium SLOScanning Laser Ophtalmoscope TTT Trans-pupilary Thermotherapy VPNVirtual private network WAN Wide area network

It is noted that the test or tests for eye disease of the presentinvention disclosed hereinbelow may also be generally referred to as theMacular computerized psychophysical test (MCPT) hereinafter.

FIG. 1 is a schematic diagram illustrating a system for carrying out aneye test to detect an eye disease according to one embodiment of theinvention. A subject 100 performs an eye test using a computer system105. The computer system 105 may comprise a computer 110, a displaydevice 115 having a screen 112 and one or more computer input devicessuch as a keyboard 120 or a computer mouse 125. The computer system 105may communicate over a communication network schematically indicated bythe cloud labeled 130. The network 130 may be, for example, theInternet, a local area network (LAN), a wide area network (WAN), anIntranet, a private area network (PAN), the public service telephonenetwork (PSTN), virtual networks implemented over the Internet, otherprivate and/or commercial communication networks, or any other suitabletype of communication network known in the art.

A processor 135 in a network server 140 stores data relating toexecution of an eye test to be performed by the subject 100 to bedescribed in detail below. The eye test is communicated from the server140 to the subject's computer 110 over the network 130. The subject 100inputs responses to the eye test using one or more of the computer inputdevices such as the keyboard 120 or the mouse 125. The subject'sresponses are communicated over the network 130 to the processor 135,and stored in the memory 145. The processor 135 is configured to analyzethe subject's response, to make a diagnosis of the subject's conditionsand to recommend future follow-up or recommend prompt examination, allin real time, for the subject.

The diagnosis and recommendation may be communicated over the network130 to the subject's computer system 105 and/or to a terminal 150 of ahealth care provider 155. The processor 135 is also configured to storein the memory 145 dates on which the subject is to perform an eye testexecuted by the processor 135. If, for example, the subject 100 has beeninstructed by the health care provider 155 to perform the test once perweek, the processor 135 may send a message over the communicationnetwork 130 when 10 days have elapsed since the last time he took thetest, informing the subject of his failure to take the test asinstructed. A similar message may be sent to the health care provider155. A responsible individual may be designated, in such a case, tocontact the subject 100, for example, by telephone to clarify why thesubject 100 has not performed the test as instructed and to impress uponthe subject the importance of performing the test as indicated.

“Moving Pattern” Test Method

The method disclosed hereinbelow is based on the presentation of a firstpattern at a first location on the surface of a display device (such as,but not limited to the screen 112 of the display device 115) to thepatient or the test subject. After the patient fixated on a fixationtarget presented on or adjacent to the first pattern, the first patterndisappears from the first location of the display device and a secondpattern is presented at a second location on the display device. Thesecond pattern may be identical to the first pattern (except for thefact that it appears at a different location on the display device) orit may be different from the first pattern by having one or moreportions thereof changed or altered, or, preferably, transiently changedor transiently altered.

Such changes or transient changes or alterations may include distortionof the shape or elimination of one or more portions of the firstpattern, or changes in the color or appearance of one or more portionsof the first pattern. Because the first pattern is made to disappearfrom the first location on the display device and the second patternappears at a second location of the display device different than thefirst location, the patient or test subject may visually perceive thisas a movement or jump of the pattern from the first location to thesecond location on the display device. In other words, the patient mayperceive a pattern “jumping” on the screen of the display device from afirst to a second location even though the pattern does not actuallymove on the display device (the pattern actually disappears from a firstlocation on the display device and appears at a second location on thedisplay device). This is why this particular embodiment of the testingmethod is referred to as the “moving pattern” or “jumping pattern” testhereinafter.

FIG. 2 is a schematic flow chart diagram illustrating a method ofexecuting an eye test for detecting an eye disease using a system suchas the system illustrated in FIG. 1, in accordance with an embodiment ofthe present invention.

FIG. 3 schematically illustrates selected exemplary screenrepresentations including exemplary test patterns which may be presentedto a tested subject, in an exemplary embodiment of the testing method ofthe present invention, and selected schematic representations of how thetest patterns may be perceived by a tested subject in selected stages ofthe testing.

FIG. 3 includes schematic screen diagrams 300, 320, 330 and 360 (alsoreferred to as screens 300, 320, 330 and 360 hereinafter) whichschematically illustrate the patterns displayed on the screen 112 of thesubject's display device 115 at various different exemplary steps of theeye test performed by the system illustrated in FIG. 2, and schematicscreen diagrams 340 and 350 (also referred to as screens 340 and 350hereinafter) which schematically illustrate the possible appearance ofthe screen 112 as may be perceived by the tested subject at someexemplary steps of the eye test. It is noted that screen 300 of FIG. 3which does not include test patterns, schematically represents apossible log-on screen which may be presented to the test subject.

It is noted that the exemplary schematic screens 300, 320, 330, 340,350, and 360 of FIG. 3 are schematically drawn for illustrative purposesonly and are not drawn to scale. Additionally, the sizes of the variouspatterns, pattern segments and fixation targets are not drawn to scale,and their sizes and their relation to the screen size are arbitrarilyshown for illustrative purposes only.

Turning to FIG. 2, in step 200, the subject 100 may log onto thecomputer system 105. The processor 135 may cause log-on screen 300 to bedisplayed on the subject's display device 115 (step 205). The log-onscreen 300 prompts the subject to input his name into a field 302 and toinput a previously assigned password into a field 304 for accessing theprocessor 135. In step 210 the subject inputs his name and passwordusing computer input devices such as the keyboard 120 or the mouse 125.The processor 135 then checks whether the inputted name and password arestored in the memory 145 (step 215). If the inputted name and passworddo not match a corresponding name and password which are stored in thememory 145, the processor 135 determines whether the number of attemptsthe subject has made to input a name and password is less than apredetermined number of attempts such as, for example, three attempts(step 220). If yes, the process returns to step 205. If no, the processterminates.

If at step 215 the processor determines that the name and password arein the memory 145, the process continues in step 248 by the subjectbeing instructed to cover an eye, so that the test is performed usingone eye only. The subject may be instructed to cover an eye bydisplaying appropriate text (not shown) or a drawing (not shown) or anicon (not shown), or a graphic element (not shown) or any combinationthereof on the screen of the display device 115.

It is noted that the tested subject 100 may be asked to cover a specificeye (for example, the subject may be asked to cover the right eye and toview the screen 112 with the uncovered left eye for testing the lefteye). In this way the computer system 110 may automatically record thatthe left eye is being tested. However, the test may also be performedwith both eyes open as a selected eye is being tested. Alternatively,the tested subject 100 may be asked to mark or input or otherwiseindicate which eye is to be tested, such as, for example, by clicking acursor on one of two boxes (not shown) which may be presented on thelog-on screen 300 or on any other suitable screen presented to thesubject before the test begins. In such a case the test results may belabeled as taken from the eye selected by the subject 100.

In step 250 a form screen 320 is displayed in which a pattern, such asthe segmented line 322, is displayed. This is by way of example only,and other suitable patterns may be used within the scope of theinvention. The pattern may comprise a single component, or may compriseseveral components, which may or may not be all identical. Thus, thepattern may comprise several lines, one or more circles, lines andcircles together, or any other suitable combination of pattern elements,including but not limited to one or more straight lines, dotted lines,curved lines, linear or non linear segments, dots, and other variousgeometrical patterns such as but not limited to circles, arcs,rectangles, squares, triangles and the like. The screen 112 of thedisplay device 115 may display a visually noisy background to thedisplayed pattern. The line 322 may be composed of several shortsegments 229 separated by gaps 227. Alternatively, the displayed linemay be continuous (not shown).

Preferably, the length of the line 322 is such that when the testedsubject's eye is at a distance of approximately 50 centimeter from thescreen 112 of the display device 115, the length of the line 322corresponds to a cone angle of 1-20°. It is, however, noted that otherdifferent cone angles and other different viewing distances (smaller orlarger than 50 centimeters from the screen 112) may be used.Additionally, it may be possible, in accordance with other embodimentsof the invention, to use “virtual reality” goggles worn by the patientwhich may have different screen sizes and may be disposed at a differentdistance from the patient eye.

It is noted that while in most tests the length of the lines usedcorresponded to a cone angle of 14°, other different line lengths may beused. At these viewing conditions, each of the gaps 227 between thesegments 229 (the distances separating two adjacent segments 229) maycorrespond to a cone angle of between 1 minutes arc to about 2° (twodegrees). Other different line lengths and gap sizes may however also beused. For example, if the test pattern is a continuous line there are nogaps.

It is also noted that if test patterns which comprise a continuous lineare used, no segments are used and there are therefore no gaps.

If the pattern includes two or more parallel lines, the spacing betweenthe lines corresponds, preferably, to a cone angle from about 10 toabout 600 minutes arc. The test patterns may be horizontal patterns suchas, but not limited to, the horizontal line 322 illustrated in screen300, but may also be vertical patterns such as but not limited to avertical segmented line (not shown) or slanted patterns such as, but notlimited to, a slanted segmented line (not shown). A fixation target 228may be displayed on the screen adjacent to one of the segments 229. Thefixation target may be a circular pattern such as the circular fixationtarget 228 of screen 320 of FIG. 3, or may have any other shape orpattern suitable for serving as a fixation target to focus the testedeye thereon, such as, but not limited to, a square pattern, a triangularpattern, or any other suitable pattern which is suitable for functioningas a fixation target.

It is noted that while the fixation target 228 illustrated in FIG. 3 isa circular pattern which appears close to the middle segment of the line322, other different forms of the fixation target may be used. Forexample, the fixation target may be implemented as a hollow (unfilled)circle (not shown) surrounding the middle segment of the line 322 orsuperimposed thereon, or as any other suitable pattern which ispositioned close to or is superimposed upon the line 322.

Generally, the shape of the fixation target may depend, inter alia, onthe shape and dimensions of the test pattern which is being used in thetest. The fixation target may have the same color of the test pattern(such as, for example, the segmented line 322) or may have a differentcolor than the color of the test pattern. In accordance with anothervariation, the fixation target may be the central (middle) segment ofthe line 322, in which case the middle segment may or may not have acolor which is different than the color of the remaining segments 229 ofthe line 322, in order to make it easily identifiable by the testsubject.

In the example in which a single segmented line serves as the testpattern, the subject may be instructed to bring a cursor 225 appearingon the screen to the fixation target 228. In order to aid the subject,the movement of the cursor 225 may be restricted to a line (not shown)which is parallel to the line 322 so that the cursor 225 always pointsto one of the segments 229.

The subject 100 may be asked (for example, by an instructor, a physicianan ophtalmologist or any other person training the subject in performingthe test) or otherwise instructed (such as for example by displayingappropriate messages or text an the screen 112 of the display device115) to point the cursor 225 at the fixation target 228. The subject 100may perform this pointing in step 255 by using a computer device such asthe keyboard 120, or more preferably the mouse 125. Other pointingdevices may also be used for pointing, such as but not limited to, akeypad, a digitizing tablet in conjunction with a stylus, or a finger, alight pen in conjunction with a touch sensitive screen or a touchsensitive display device, a joystick or any other suitable pointingdevice or suitable input device or computer input device known in theart.

The fixation target 228 may be sized so that it is large enough to beseen by the patient or test subject, but small enough so that bringingthe cursor 225 to the fixation target 228 is a demanding task for thetest subject. This causes the subject to fixate his vision on thefixation target 228. Upon bringing the cursor to the segment 229, thesubject may provide a suitable indication that he has positioned thecursor 225 to point at the fixation target 228. For example, the patientor test subject 100 may provide the indication by clicking on the mouse125 or by depressing a predetermined key on the keyboard 120 (step 260).This input may serve as an indication or a verification that visualfixation has been achieved. It is noted that the size of the fixationtarget 228 may depend, inter alia, on the distance of the tested eyefrom the screen 112.

It is noted that if the subject is using a pointing device and/or aninput device which is different than the mouse 125 or the keyboard 120,the subject may indicate fixation on the fixation target 228 byperforming any other suitable action. For example, if a touch screen(not shown) is used as an input device, the subject may touch the touchscreen (not shown) with a light pen (not shown), or with a stylus (notshown) or with a finger (not shown) at the position at which thefixation target is displayed. Other suitable forms of indicating orconfirming fixation may be used, depending, inter alia, on the inputdevice or pointing device which is being used.

When the subject signals (for example, by clicking a button on the mouse125, or by any other suitable way) that the cursor 225 is positioned topoint at the fixation target 228, indicating that his vision is fixatedon the fixation target 228, the line 322 is made to disappear from thescreen 320 (step 265). After a predetermined delay time interval (forexample a delay interval in the range of 0 to 200 milliseconds), asecond pattern such as the segmented line 332 is made to appear(displayed) on the screen 112 at a location different than the locationof the line 322 as shown in screen 330 (step 270), so as to allow thesubject to form a perceived image of the segmented line 332. In thisexample, the segmented line 332 is similar to the line 322 but appearson the screen 112 at a location which is different than the location ofthe line 322.

It is noted that if the duration of the delay time interval is zero, theline 332 is presented on the screen 112 immediately after (or within theshort time required by the computer 100 to process the subject's inputand display the line 332 on the screen 112) the subject 100 indicatedfixation. In most of the experimental eye tests conducted in patients nodelay was used (the delay time interval was zero).

The line 332 may, for example, be parallel to the line 322. Since thesubject's vision had been fixated on the fixation target 228, the line332 will appear in the periphery of the subject's field of vision. Anydisturbance in his vision due to a retinal or choroidal lesion (such asbut not limited to a lesion caused by AMD or diabetes or by otherdifferent pathological eye conditions) may be apparent to the testsubject as a difference between the perceived image of the secondpattern and a pre-defined reference pattern, which in this example isprovided by the first pattern (the segmented straight line 322).

Additionally, or alternatively, the tested patient or subject 100 mayhave been told by a trainer (such as, for example, by an ophtalmologistor other medical or paramedical personnel) before the beginning of thetest that he or she is going to be presented with test patterns whichwill look like a segmented straight line. In such a case, the subject100 may conceive a “virtual” predetermined reference pattern which inthis particular example of the test is a conceived image of a straightsegmented line. The word “virtual” is used herein to indicate that thepredetermined reference pattern is mentally conceived by the patient ortest subject without having to actually present the patient with thetest pattern. In other words, the understanding of the patient of howthe reference pattern (such as, for example, the straight segmented lineof the example illustrated in FIG. 3) is supposed to look like may bebased on the previous visual experience of the patient or test subject.

The explanation to the patient of what the reference pattern is going tolook like may be advantageous, since in a small percentage of patientsit may happen that in the first presentation of the first test pattern(such as for example in the initial presentation of the line 322) theimage of the test pattern may fall on a lesioned retinal or choroidalregion. In such a case, the perceived image of the test pattern may bedistorted. Therefore, in such a case, the perceived image of theinitially presented line 322 is not usable as a reference pattern andthe patient may see or detect a difference between the perceived imageof the line 322 and the (virtual) reference image which the patient hasbeen told to expect.

The difference between the perceived image of any of the test patterns(including, but not limited to, the lines 322 and 332) which may bepresented to the patient and the reference pattern may be perceived bythe test subject 100 in various different ways. Thus, as the line 322 isperceived by the subject to jump or move to the new location on thescreen 112 one or more of the segments 229 of the line may seem to thesubject not to arrive at their new position on the line 332 (of thescreen 330) at exactly the same pace or contour as the other segments.In other words, one or more portions or segments of the line maytemporarily seem to lag or to move differently relative to the otherparts or segments of the perceived line. This may also be perceived bythe subject as if one or more portions of the perceived line were wavyor moved or bulged for a short while or as if one or more of thesegments or line portions deviated from the reference pattern (which isa straight segmented line, in the exemplary and non-limiting example ofFIG. 3) before assuming again the perceived appearance of the referencepattern. Additionally or alternatively, depending, inter alia, on thenature of the retinal (or choroidal) lesion present, one or moreportions or segments of the perceived image of the test pattern (suchas, for example, one or more of the segments 229 of the perceived line322) may appear to temporarily change their apparent brightness (such asbecoming brighter or becoming darker), or change their color temporarilyas the line moves or jumps, and then return to their originallyperceived brightness or originally perceived color, respectively.Additionally or alternatively, one or more of the segments 229 orportions of the test pattern may appear to momentarily or temporarilybecome blurred or smeared.

Additionally, various different combinations of these differences mayalso be perceived by the subject. For example one or more of thesegments or portions of the test pattern may appear to lag or movedifferently than the other segments or portions of the pattern and alsoto change their perceived brightness. Other different combinations ofdifferences may also be perceived by some patients.

For example, when the subject's vision is fixated at the location wherethe fixation target 228 had previously appeared (represented by thecrossed lines 342 in screen 340), a segment 344 of the line 332 mayappear to be out of line with other segments in the line 332 or may beotherwise distorted, blurred, shifted or discolored. It is noted thatthe screen labeled 340 of FIG. 3 represents the screen 112 and thepattern 332 as perceived by the tested subject. In other words, theillustrated line 332 with the shifted segment 344 is shown as perceivedby a subject or patient having a retinal or choroidal lesion and not asactually displayed on the screen 112. Thus, while the screen 330 of FIG.3 schematically represents the image as actually presented to thesubject 105 on the screen 112, the screen 340 of FIG. 3 represents theimage perceived by a subject having a retinal or choroidal lesion (inthe tested eye) after the line 332 of screen 320 is made to disappear(hidden) and the line 332 of screen 330 is presented (or displayed) tothe subject at a different location on the screen 112.

Screen 340 (of FIG. 3) illustrates a possible appearance of the line 332(of screen 330) to an individual having a retinal or choroidal lesion.The perceived line 352 of the perceived screen 340 represents the imageof the line 332 presented in screen 330 as it may be perceived by anindividual having a retinal or choroidal lesion. The segment 342 of theperceived line 352 may typically be temporarily or transiently perceivedas being out of line with other segments in the line 352. This is by wayof example only, and other differences between the perceived image andthe pre-defined reference pattern may be perceived, such as, but notlimited to, one or more segments in the second pattern appearing to thesubject as being shifted or wavy or lagging behind, or blurred, ordimming, or smeared, or bent, or otherwise distorted, or discolored.Additionally, one or more of the segments in the second pattern may beperceived by the subject to disappear or to be missing from the secondpattern. As the subject subsequently shifts his vision from the fixationtarget 228 to the presented line 332, the segment 344 in the image ofthe perceived line 352 may appear to move into alignment with othersegments in the line 332 as shown in screen 350. Thus, the line 363 ofscreen 350 (FIG. 3) schematically represents the perceived image of theline 322 as possibly perceived by the subject having a retinal orchoroidal lesion after the subject re-fixates his vision on the line332. Thus, the segment 344A schematically represents the new perceivedposition of the previously perceived segment 344 after the patientshifted his eye to refixate on the new position of the line 332. Theperceived segment 344A may now be perceived as realigned again with therest of the perceived segments of the perceived line 363.

Typically, the reason for the presented line 332 being perceived asstraight again (as illustrated in the perceived line 363 of screen 350)after the patient refixated his vision at the new position at which theline 332 appeared after the line 322 disappeared from the screen, isthat in most cases when the subject shifts his vision from the fixationpoint 228 to the new location on the screen at which the line 332appeared, after a certain time (typically a few hundred milliseconds orlonger) the “filling-in” phenomenon disclosed hereinabove may occur.

The subject, in step 275, may indicate which, if any, of the segments inthe line 332 appeared different or were perceived to behave differentlythan corresponding segments in the predefined reference pattern. Thismay be done by the subject bringing the cursor 225 to the segment orsegments that appeared to move or to blur or to distort or to disappear,or to otherwise change (the segment 344 in this example) and clicking abutton on the mouse 125 or a key on the keyboard 120, or by otherwiseperforming an action with a pointing device (not shown) or any othersuitable input device (such as, but not limited to, any of the inputdevices disclosed hereinabove and hereinafter). The data representingthe location(s) on the screen 112 of the segment or segments in theregion pointed to by the subject may thus be stored by the system (step277) in the memory of the computer system 105, and/or in the memory 145of the server 140 or by any other suitable storage means, such as butnot limited to, a fixed or removable magnetic media storage device (Harddisc drive or floppy disc drive), optical storage device,magneto-optical storage device, holographic storage device or any othersuitable storage device known in the art. This stored data may be usedto locate and/or report and/or display and/or symbolically represent (inhard copy or otherwise), the region in the subject's retina in which theretinal lesion (or an underlying choroidal lesion) is located, asdisclosed in detail hereinafter.

It is noted that the storage device or memory used for storing the testresults data may be included in or suitably linked or coupled to thecomputer system 105 or the computer 110, or the server 140.Alternatively, the storage device may be a shared device which is sharedby or accessible to one or more of the computer system 105 or thecomputer 110, or the server 140, over a communication network. Thus,while the test results data may be stored locally on the system 105,this is not obligatory and the test results may be stored elsewhere asdisclosed hereinabove.

In step 280 it is determined whether adequate mapping of the field ofvision was achieved. For example, it may be checked whether the numberof lines 322 presented to the subject is less than a predeterminednumber, such as, for example, 40 (or any other suitable predeterminednumber). If the number of lines 322 presented to the subject is lessthan the predetermined number, the process may return to step 250 and anew line 322 is presented to the subject. Steps 250 to 280 may berepeated several times, for example 40 times (or any other suitablepredetermined number of times suitable for such a test). In eachrepetition the line 332 may be presented at a different location of thescreen 112 until the region of the subject's macular visual field hasbeen appropriately mapped.

It is noted that such mapping may be achieved in more than one way. Forexample, in accordance with one preferred embodiment of the invention,after the line 332 is presented or displayed to the subject 100, and thesubject has finished marking the segments which appeared different thanthe corresponding segments of the line 322, or alternatively to mark thesegments which appeared different than the “virtual” predeterminedreference pattern (a straight segmented line mentally conceived by thesubject), the subject may visually fixate the tested eye on a fixationtarget 228A (see screens 330, 340, 350 and 360) in the vicinity of theline 332, by bringing the cursor 225 to point at the fixation target228A and clicking a button on the mouse 125 to indicate fixation asdisclosed in detail hereinabove. This may trigger the repeating of steps265 and 270 which will result in the disappearing of the line 322 andthe showing of a new line (not shown) at a new position on the screen112 which is different than the position at which the line 332 waspreviously presented. The subject may then proceed to mark any segmentsat which a difference was perceived as disclosed hereinabove. Thepresentation may be similarly continued until adequate mapping of thefield of vision has been performed.

Alternatively, in accordance with another embodiment of the presentinvention, after the line 332 is presented or displayed to the subject100, and the subject has finished marking the segments which appeareddifferent than the corresponding segments of the line 322, oralternatively to mark the segments which appeared different than the“virtual” predetermined reference pattern (a straight segmented linementally conceived by the subject), the line 332 may be caused todisappear from the screen 112, and the line 322 and the fixation target228 may be again presented to the subject 110 in the same positionsillustrated in screen 320. The subject may then again fixate on thefixation target 228 by bringing the cursor 225 to point at the fixationtarget 228 and click the mouse 125 to indicate fixation. The computer100 may then present a new test pattern (not shown) at another newposition relative to the position of the line 322 and the process mayrepeat after the subject marked any segments for which a difference wasobserved. By randomly or pseudo-randomly selecting a new line positionfor each new repetition the process may thus achieve adequate mapping ofthe desired macular area.

It is noted that if the first test pattern (such as for example thestraight segmented line 322) which is presented to the subject happensto be projected on a region of the retina which is lesioned (at theretinal or the choroidal level), the subject 100 may initially perceivethe pattern to be distorted or modified but after a certain time thetest pattern may be perceived to be identical with the predeterminedreference pattern (such as for example a straight non-distortedsegmented line due to the “filing in” phenomenon disclosed hereinabove.In such a case, the subject 100 may indicate or mark the location of theinitially perceived distorted or modified region or component of thefirst test pattern, by using the mouse 125 and the cursor 225 asdisclosed hereinabove.

Alternatively, the subject 100 may be instructed (before or during thetest) to ignore the initially perceived distortion or modification andto proceed to perform the fixation on the fixation target 228 asdisclosed hereinabove by bringing the cursor 225 to point at thefixation target 228 and clicking a button on the mouse 125. When thesecond test pattern, such as the line 332 is then presented at anotherlocation on the screen 112 (see screen 330 of FIG. 3), the subject 100may temporarily perceive a modification or distortion as the subject 100shifts his vision from the fixation target towards the location of newlypresented test pattern (which in this example is the location of theline 332 of screen 330 of FIG. 3). Therefore, in such cases in which theimage of the first test pattern falls on a lesioned retinal area, thesubject may perceive a distortion or modification in each of therepetitions or iterations of the test, irrespective of the location atwhich the second test pattern is presented on the screen 112. Thedistortion will be perceived after the patient shifted his vision fromthe fixation target towards the test pattern presented at the newlocation due to the fact that the shifting causes the image of the newlypresented test pattern to be projected on the lesioned retinal area.Because of this phenomenon, the subject may mark a distortion ormodification on all the second test pattern repetitions, and all of themarked distortions will tend to be marked at positions along the testpattern which approximately correspond to the position of the distortionor modification which was initially perceived at the first time ofpresentation of the first test pattern due to the presence of theretinal lesion (or of a choroidal lesion).

It is noted that if the test results do exhibit such an approximate“alignment” of multiple markings of perceived distortions ormodifications at approximately similar positions on the test pattern,irrespective of the location of the presented second test patterns, thismay be taken as an indication that there is at least one suspectedretinal (or choroidal) lesion at a position in the retina on which theimage of first test pattern was projected.

It is further noted that while the presence of a retinal lesion may bedetected in the above case, it may be advisable to test the same eye ofsubjects exhibiting such a spurious marking “alignment” using the “flashtest” embodiment of the invention as disclosed in detail hereinafter,since this test does not show this spurious marking “alignment”phenomenon.

It is noted that while it is possible to perform the testing by mappingthe field of view of the patient using only horizontal line patterns(such as the line 322) and moving the horizontal line patternsvertically to different positions on the screen 112, the mapping mayalso be performed using vertical lines (not shown in FIG. 3) which maybe moved horizontally to different positions on the screen 112. It mayalso be possible to use a plurality of orthogonal horizontal andvertical lines in the same mapping test, in which case the mappingcoverage of the field of vision may resemble a grid of intersectinglines (not shown).

Furthermore, the mapping of the field of view may also be done using aseries of lines that are inclined at an angle to the horizontal orvertical orientation (slanted lines), or combination of series ofslanted lines which may intersect each other either orthogonally ornon-orthogonally, such that if these lines were all displayed at thesame time on the screen 112 they may form a grid of intersecting lines(not shown).

It is noted that in step 280 it is checked whether adequate mapping ofthe field of vision of the tested eye has been achieved. For example, ifthe location of presentation of the test pattern is different at eachrepetition or iteration of the test, adequate mapping may be ensured bychecking that the number of lines presented to the subject has reached apredetermined number of iterations ensuring that data has been collectedwhich suitably covers or maps the entire field of vision at a desiredresolution.

Other different methods may however also be used to check adequatemapping. For example, if the testing of each location needs to berepeated more than one time and the location of presentation of testpatterns is randomly or pseudo-randomly selected, the locations ofperformed tests may be compared with a look-up table to verify that thedesired number of test repetitions for each test pattern location hasbeen performed. If adequate mapping has not been achieved the processmay return control to step 250 to present the next test pattern.

If adequate mapping of the field of vision of an eye has been achieved,the process may proceed by determining whether only one eye has beenexamined so far (step 282). If only one eye has been examined, thesubject may be instructed to uncover the non-examined eye and to coverthe examined eye (285). The process may then return to step 250 with thesubject testing his other eye as disclosed in detail hereinabove. Ifboth eyes have been examined, the process may terminate (step 290).

The position of the line 322 presented or displayed to the subject onthe screen 112 may thus be varied in order to appropriately cover themacular area at a desired resolution so as to detect lesioned retinalregions. It is noted that in accordance with one preferred embodiment ofthe invention, the mapping may be performed more than once, and that thecentral part or foveal region of the macular area of the retina may alsobe mapped at a higher resolution than the rest of the macular area. Thismay be accomplished by presenting to the subject test patterns such asthe line 322 at locations which are relatively close to one another onthe screen 112. This may result in higher lesion mapping resolution inthe foveal region. In addition, more test patterns may be presented inareas in the mapped visual field, where there are defects, than in otherareas in the mapped visual field.

Reference is now made to FIGS. 4A-4B which are schematic diagramsillustrating some exemplary types of line series which may be useful formapping retinal lesions in accordance with some exemplary embodiments ofthe present invention.

FIG. 4A schematically represents a mapping grid which may be formed ifall the linear test patterns used in the test were to be simultaneouslypresented on the screen 112. The grid 500 thus formed may includeparallel vertical lines, such as for example the vertical lines 502A,502B, 502C, 502D, and 502E and parallel horizontal lines, such as forexample the vertical lines 504A, 504B, 504C, 504D, and 504E. It is notedthat the horizontal lines need not be equally spaced from each other.For example while the line pairs 502A and 502B, 502B and 502C, and 502Cand 502D may be separated from each other by a cone angle D1, the linepairs 502D and 502E may separated from each other by a cone angle D2.Preferably D1 is larger than D2, such that the density of grid lines atthe central region of the grid 500 is higher than the density of thelines at more peripheral regions of the grid 500. This may enablemapping of the central foveal region at a higher mapping resolution thanthe mapping of more peripheral foveal regions.

It is noted however, that the horizontal and vertical lines of the grid500 may also be equally spaced from each other or may be arrangeddifferently than the arrangement of the lines illustrated in FIG. 4A.Furthermore, it is noted that while the lines of the grid 500 may becontiguous lines as shown in FIG. 4A (for the sake of clarity ofillustration), the lines of the grid 500 may also be segmented lines(not shown) or dotted lines (not shown) or the like. Orthogonal ornon-orthogonal slanted lines may also be used (not shown) to map theretinal visual field.

The grid used for mapping may also include only the horizontal linesshown in grid 500 or only the vertical lines of grid 500. Furthermore,It is noted that the number and the density of the lines shown in FIG.4A is only shown by way of example and the number of the lines as wellas the separation between the lines may be modified or changeddepending, inter alia, on the required retinal mapping resolution.

FIG. 4B schematically represents a mapping grid 510 which may be formedif all the linear test patterns used in the test were to besimultaneously presented on the screen 112. The grid 510 thus formed mayinclude a plurality of lines 512-517 which intersect at a point. Whilethe lines 512-517 are illustrated as having identical lengths, theirlengths may also vary. The angles α1, α2, α3, α4, α5, and α6 may beidentical to each other and may be all equal to 60°. It is noted,however, that the number of lines in the grid and the angle at whicheach line is inclined relative to the horizontal line 515 may vary andmay be different than the values illustrated in FIG. 4B. Additionally,the number of the lines may vary such that the grid may include more orless than the six lines 512-517. While the lines 512-517 are illustratedas contiguous (for the sake of clarity of illustration), the lines mayalso be segmented or dotted lines, or the like.

It is furthermore noted that many variations and permutations of thetest patterns of the invention are possible and are all considered to bewithin the scope and spirit of the present invention. Similarly, thenumber of the test patterns forming the mapping grid may vary as maytheir separation from each other, their angular inclination within themapping grid.

It will be apparent to those skilled in the art that the exemplarymapping grids 500 and 510 do not represent the form or shape of a singletest pattern, but are rather virtual representations of the images thatwould result if all the test patterns of exemplary possible tests wereto be projected simultaneously on a surface.

In accordance with another embodiment of the invention, it is alsopossible to present to the subject test patterns which include adistortion or other modification of the predefined reference pattern.For example, while the line 332 of screen 330 of FIG. 3 comprisessegments which are all arranged or aligned in a straight line, a line362 actually having a displaced segment 364 may also be presented to thesubject on the screen 112 as illustrated in screen 360 of FIG. 3.

The displaced segment 364 may be transiently presented at it's displacedposition, for example, for a duration of up to about 300 milliseconds,after which the displaced segment 364 may be realigned with the othersegments of the line 362, but other different suitable presentationduration time values may also be used.

It is noted that while in accordance with one embodiment of the presentinvention, the displaced segment 364 may remain displaced for the entireduration of presentation of the line 362, preferably, the segment 364 isonly transiently displaced as shown and is then realigned with theremaining segments of the line 362 for the remaining part of thepresentation of the line 362. This method of presentation may bettermimic the characteristics of the image perceived by patients which havea retinal or choroidal lesion when a segmented line similar to thesegmented line 322 is projected on a region having a retinal orchoroidal choroidal lesion as disclosed in detail hereinabove.

Generally, test patterns, such as for example the line 362 of screen 360(FIG. 3) may be regarded as test patterns which include an intentionallyintroduced distortion which may be similar to distortions which may beseen or perceived by a patient having a retinal or choroidal lesion whena non-distorted test pattern (such as, but not limited to the line 332of screen 330) is presented to the patient. Such test patterns includinga distortion may also be referred to hereinafter as “artificiallydistorted” test patterns. The presentation of such artificiallydistorted test patterns may be used, inter alia, to ascertain that thesubject is aware of the visual distortion associated with a retinal orchoroidal lesion, and that his responses reliably reflect the perceivedappearance of lines presented to him.

It is noted that while in the exemplary artificially distorted line 362illustrated in screen 360 of FIG. 3 only one segment 364 is shifted ordisplaced relative to the other segments of the line 362, various otherdifferent types of distortions may be used. In accordance with otherexemplary embodiments of the invention such distortions may include, butare not limited to, displacing or misaligning more than one segmentrelative to the rest of the segments (not shown) of the line 362,transiently or briefly displacing or misaligning one or more segmentsrelative to the rest of the segments within part of the duration ofpresentation of the line 362, tilting or changing the orientation of oneor more segments relative to the orientation of the remaining segments(not shown), bending or otherwise changing the shape of one or moresegments, removing one or more of the segments (not shown), blurring oneor more of the segments (not shown), changing the hue or color orbrightness of one or more segments of the test pattern (not shown), orintroducing other types of alterations to the test pattern which mayresemble distortions or alterations which may be perceived by a personhaving a retinal lesion when such a person is presented with anon-distorted test pattern or reference pattern, such and other changesor distortions or modifications of the test pattern may, preferably, betransient changes but similar non-transient changes may also be used.

It is noted that if the test patterns used in the test arenon-segmented, such as for example if the test pattern comprises acontiguous (non-segmented) straight line (not shown), the artificiallydistorted test patterns may include, but are not limited to, bending oneor more portions of the contiguous line such that these portions are notstraight (for example, such distorted portions of the test pattern maybe curved or wavy), blurring or smearing one or more portions of thetest pattern (not shown), hiding (not presenting) one or more portionsor parts of the test pattern (not shown) or changing the hue or color orbrightness of one or more portions of the test pattern, or the like.Other suitable visually perceivable types of distortions or alterationsof test patterns may also be used.

The presentation of such artificially distorted or otherwiseintentionally altered or modified test patterns to the patient or testsubject may also be advantageously used to detect cases in which thepatient is not paying attention to the test patterns due to fatigue ordue to any other reason. This may enable the assessment of the degree ofreliability of the test result. For example, if the patient does notreliably and/or accurately report the presence of the distortion oralteration in such artificially distorted or otherwise altered testpatterns presented to him during the testing, this may be taken as anindication of a problem and may indicate a possible need to repeat thetest or alternatively to label the test results as unreliable.Additionally, the degree of correlation between the location of thedistortion or alteration on the presented test pattern and the locationof the distortion or alteration perceived and marked (or reported) bythe patient may be used to assess the accuracy of perceiving and/or ofthe reporting of the location of the distortion or alteration by thepatient or tested subject.

It is noted that in the exemplary screen 320 of FIG. 3, the segmentedline 322 may be regarded as a pre-determined “reference pattern” of thetest. The patient may be asked and/or trained to relate to the perceivedimage of the presented straight segmented line 322 as the referencepattern against which to compare the perceived images of the laterpresented test patterns. When the test is first presented to a patient,the patient may be told by the trainer or the individual administeringthe test that he is about to be shown a straight segmented line (or anyother reference test pattern which is being used for the test). In thisway, the patient becomes aware of the reference pattern against which heis expected to compare the perceived images of the test patterns whichare going to be presented to him as the testing proceeds. It is notedthat the patient may also be told before the testing begins that he isto be presented with straight segmented lines (without initiallypresenting to him such a line) and asked to compare the perceived imageof each of the lines presented to him with a reference pattern which isa straight segmented line.

It is noted that the testing method of the present invention is notlimited to the “moving pattern” testing method disclosed hereinabove,and may be modified in different ways, which are considered to be withinthe scope of the present invention.

“Flash Test” Method

In this embodiment of the invention, a fixation target is presented tothe tested individual on a display device, such as but not limited tothe screen 112 of the display device 115 (FIG. 1). After the testedpatient has fixated on the fixation target, a test pattern is brieflypresented (flashed) at a first location on the display device for a timeduration which is sufficient to allow the patient to perceive an imageof the presented test pattern. The image perceived by the patient inalso referred to as a “perceived image” of the test pattern. The patientmay then be requested to indicate whether he or she detected adifference between the perceived image of the presented test pattern anda reference pattern.

The tested patient may be informed by the trainer, or ophtalmologist orthe person delivering the test, before the test is performed, that he isgoing to be presented with patterns similar to or different than areference pattern. The patient may or may not be actually presented withthe reference pattern before the test begins. For example, if thereference pattern is a straight segmented line, the patient may beverbally told that he is going to be presented with a variety of testpatterns that may be similar to or may be different from a straightsegmented line, without showing the patient a straight segmented line(which is the reference pattern in this non-limiting exemplary test)prior to the presentation of the actual test patterns to the patient. Insuch a case, the reference pattern is based on the prior acquaintance ofthe patient with the reference pattern which is used. In other words,previous knowledge of the patient of how a straight segmented line looksis relied upon.

It is also possible (though not obligatory), however, to present thereference pattern to the patient before the actual test patterns arepresented, in order to give the patient an idea of how the referencepattern is supposed to look. While this may help the patient tounderstand and familiarize himself or herself with the form of thereference pattern, it is not a necessary part of the test, since mostpatients may adequately perform the test just by being told verballywhat the reference pattern is, without being presented with the actualreference pattern prior to the presentation of the test patterns.

After the patient is presented with a test pattern, if a difference wasdetected by the patient between the pattern perceived by the patient asa result of the presentation of the test pattern and the referencepattern, the patient may indicate the region or regions or segments orcomponents of the perceived pattern at which a difference or differenceswere noticed. The presence and the location of the difference(s) whichare detected and indicated by the patient may be stored for furtherprocessing and analysis as disclosed hereinabove. This procedure may berepeated several times while changing the location of the test patternrelative to the fixation target on the screen 112. The number ofrepetitions and the location of the presented test patterns are suchthat a suitable area of the visual field of the tested eye of thepatient is mapped for detection of possible retinal lesions orpathologies.

Reference is now made to FIGS. 5A-5J which are schematic diagramsillustrating the patterns displayed on the screen 112 of the subject'sdisplay device 115 at various different exemplary steps of anotherembodiment of an eye test performed by the system illustrated in FIG. 1,and the possible appearance of the test patterns as they may beperceived by the test subject at some exemplary steps of the eye test.

In performing the flash test, the patient or test subject may bepositioned before the screen 112, with the distance of the tested eyebeing preferably approximately 50 centimeters from the screen 112. Otherdifferent distances may however also be used depending, inter alia, onthe dimensions of the screen 112, and on the size of the displayed testpatterns.

The “flash test” method may begin by presenting to the patient or testsubject one or more log-on screens, such as, but not limited to, thescreen 300 schematically illustrated in FIG. 3. Other additional screens(not shown) may also be presented for entering other patient demographicdata or the like. Once the patient identity has been established, screen370 (FIG. 5A) may be presented to the patient.

A fixation target 372 is displayed on the screen 112. The fixationtarget 372 may be a circular pattern or may be any other suitably shapedpattern as disclosed in detail hereinabove for the fixation target 228of FIG. 3. A cursor 373 may also be displayed on the screen 370. If thepatient is trained to take the test, the trainer or test supervisor mayexplain to the patient that he or she should cover one eye (by hand orby using a suitable eye occluding device or patch), look at the screen370 with the non-covered eye, and bring the cursor 373 to point at thefixation target 372.

Preferably, but not obligatorily, the movement of the cursor 373 may berestricted to the horizontal direction. For example, in accordance withone possible implementation of the method, the tip of the arrowhead-likepointing part 373A of the cursor 373 may be pointed upwards and it'smovement may be restricted along an imaginary non-visible horizontalline (not shown) intersecting the fixation target 372. The patient maybring the cursor 373 to point at the fixation target 372 by using amouse or any other suitable pointing device, as disclosed in detailhereinabove for the moving line method.

Similar to the fixation target 228 of FIG. 3, the fixation target 372may be sized so that it is large enough to be seen by the patient ortest subject but small enough so that bringing the cursor 373 to thefixation target 372 is a demanding task for the test subject. Thiscauses the subject to fixate his vision on the fixation target 372. Uponbringing the cursor 373 to the fixation target 372, the subject mayprovide a suitable indication that he has positioned the cursor 373 topoint at the fixation target 372. For example, the patient or testsubject may provide the indication by clicking on a button of the mouse125 or by depressing a predetermined key on the keyboard 120 (or bysuitably using any other suitable pointing device known in the art ordisclosed hereinabove). This patient input may serve as an indication orverification that visual fixation on the fixation target 372 has beenachieved.

After the patient indicates fixation as disclosed hereinabove, a testpattern in the form of a segmented straight line 382 is presented to thepatient (see screen 380 of FIG. 5B). It is noted that while theexemplary test pattern illustrated in FIG. 5B is a segmented straightline 382 as disclosed hereinabove for the moving line test method, othertypes of different test patterns (not shown) may however also be used.The segmented straight line 382 may be presented on the screen 112immediately after the patient clicks the mouse 125 or may be presentedafter a delay. If a delay is used, the duration of the delay maypreferably be in the range of approximately 0-200 milliseconds, butother higher values of the duration of the delay may also be used. Thesegmented straight line 382 may be displayed on the screen 112 for ashort duration. Preferably, the duration of presentation of the testpattern (the line 382) on the screen 112 may be in the range ofapproximately 100-160 milliseconds. It was practically found that mostpatients perform the test well with the test pattern presentationduration in this range which enables to keep the duration of a test inthe approximate range of 2-3 minutes (for a typical test including thepresentation of 23 vertical segmented lines and 23 horizontal segmentedlines).

It is noted that duration of presentation may also be shorter or longer.Typically, a duration of approximately 10-20 milliseconds may be on thethreshold of observation for most patients. Thus, presentation durationvalues which are longer than 10-20 milliseconds may have to be used formost patients. The threshold of observation may, however, vary, interalia, with the patient's age, visual acuity, or the like.

It is also noted that the test pattern presentation duration may also belonger than 160 milliseconds, but this may increase the overall testduration.

One advantage of the relatively short duration of the presentation ofthe test pattern (also referred to herein as “flashing” of the testpattern) may be that the eye/brain system of the patient may not haveenough time to “fill-in” the distorted or missing or different parts ofthe perceived image of the test pattern, as it may do when the testpattern is static or is presented for a relatively long period of time.This may advantageously reduce or prevent such “filling-in” phenomenadisclosed in detail hereinabove, which may decrease the probability ofthe patient not observing or not detecting (and therefore not reporting)a difference in the appearance of the perceived test pattern (as mayoften occur in the use of the Amsler test).

It may be further explained to the patient (either before performing thetest or while the test is being taken) that he is going to be presentedwith test patterns on the screen 112. The patient may, for example, betold that the presented test patterns are going to be segmented straightlines, and that the reference pattern against which he is to comparewhat he actually perceives on the screen 112 is a segmented straightline.

The patient may further be instructed that if he or she detects anydifference between the perceived form of the presented test pattern orof one or more parts or portions thereof and the reference pattern(which is a straight segmented line in the non-limiting exampleillustrated in FIGS. 5A-5J), he or she is requested to indicate theapproximate location of the part or parts which were perceived to differfrom the reference pattern, as is disclosed in detail hereinafter.

For example, it may be explained to the patient that one or more of thesegments of the straight line may deviate from linearity or may appearto move, or may appear wavy, or may appear to bulge or to deviate or tobe distorted such that they are not perceived to be arranged as astraight line, and that other differences may also be observed such as,for example, a movement of one or more segments or parts of theperceived image of the test pattern relative to other parts or segmentsor portions of the perceived test pattern, or a dimming or brighteningof some segments relative to the rest of the segments, or a change inthe hue or color of some segments relative to the hue or color of othersegments, or a fuzziness or blurring of one or more segments relative tothe other segments, or that one or more segments or portions of thesegmented straight line may appear to be missing, and that otherdifferences may also be perceived.

FIG. 5C schematically illustrates a screen 390 which is a representationof how the presented screen 380 (FIG. 5B) may be perceived by a patienthaving a retinal lesion while the patient's tested eye is fixated on thefixation target 372. The perceived image perceived by the patient may bea distorted segmented line 392 (FIG. 5C). In the perceived distortedline 392, the segments 392A, 392B, and 392C are perceived as shifted ordistorted, or moving, or forming a bulge such that they are not arrangedin a straight line. This may be due to the presence of a retinal lesion.

After the presentation of the test pattern is terminated, the testpattern 382 disappears from the screen 112 by terminating the displayingthereof on the screen 112. The patient may then indicate or mark theapproximate location of the perceived region of difference or distortionon the perceived image. This marking or indicating may be performed, forexample by the patient using the mouse 125 to move the cursor 373 to theregion of the screen 112 where the difference was observed or detected.FIG. 5D illustrates the appearance of a screen 400 after the patientmoved the cursor 373 to the approximate position on the screen at whichthe patient observed the distortion in the perceived image illustratedin FIG. 5C. This position roughly matches the region where the segments392A, 392B, and 392C (of FIG. 5C) were perceived by the patient asshifted or distorted. After the positioning of the cursor 373 at theapproximate position at which the difference or distortion was observedthe patient may click a button on the mouse 125. The computer system 105may thus determine from the position of the cursor 373 in screen 400(FIG. 5D) the location on the test pattern at which a difference ordistortion was observed or detected by the patient in the perceivedimage 392 of the test pattern 382 which was presented in screen 380 (ofFIG. 5B). This location may be stored as data in the computer system105.

It is noted that while in screens 370 and 380 (of FIGS. 5A and 5B,respectively) the movement of the tip 373A of the arrowhead-like cursor373 was restricted along an imaginary, non-visible, horizontal line (notshown) intersecting the fixation target 372, after the termination ofthe presentation of the test pattern 382, the cursor is preferably notrestricted and may be moved to any point on the screen 400.Alternatively, the moving of the cursor 373 may remain verticallyrestricted as disclosed hereinabove, in which case the patient may markthe location of the observed distortion or difference by moving thecursor 373 horizontally (not shown) until it reaches a location which isabove or below the region at which the difference or distortion wasobserved on the perceived test pattern, (depending on whether thelocation of the appearance of the test pattern was below or above thefixation target 372, respectively).

The computer system 105 may thus store data representative of thelocation (or locations) marked by the patient. In accordance with oneexemplary embodiment of the invention, the data may include the positionof the test pattern 382 on the screen 380 and the position on the testpattern 382 which is equivalent to the horizontal position marked by thecursor 373 on the screen 400 (which is indicative of the location whichwas marked by the patient as the approximate region of the distortionperceived by the patient). Other different methods of storing the datamay also be used as may be apparent to those skilled in the art.

It is noted that the computer 105 may also store other information ordata associated with the presented test pattern. For example, the storeddata may include, but is not limited to, the number of the test pattern(which may be indicative of the order of presentation of the particulartest pattern within the test), the orientation of the test pattern (forexample, vertical or horizontal, or the like), or any other data relatedto other parameters of the test pattern.

After the marked position of the distortion is stored, the patient mayinitiate the presentation of a new test pattern by repositioning thecursor 373 to point at the fixation target 372 and clicking a button onthe mouse 125 as disclosed for screen 380 (of FIG. 5B) to indicate theachieving of fixation. This may cause the presentation of a new testpattern 402 as illustrated in the screen 410 of FIG. 5E. In thisexemplary screen, the test pattern 402 is briefly presented at a newlocation on screen 410, different than the location of the test pattern382 on screen 380 (FIG. 5B). The patient may perceive the presented testpattern 402 as a segmented straight line with no distortion (or nodifference from the reference pattern) if there is no retinal lesion inthe retinal region on which the image of the test pattern 402 isprojected when the patient maintains visual fixates on the fixationtarget 372. The patient does not mark any position on the screen 410since no distortion or difference from the reference pattern wereobserved by the patient. The patient may then proceed by visuallyfixating on the fixation target 372 and clicking on the mouse 125 toinitiate the presenting of a new test pattern (not shown).

It is noted that in accordance with one embodiment of the invention, thecursor 373 may be automatically shifted to a new position away from thefixation target 372 following the termination of the presentation of thetest pattern. This may be advantageous since it may force the patient tobring the cursor 373 again to point at the fixation target 372 which mayensure proper visual fixation before the presentation of each new testpattern. This however is not mandatory, because it may be possible totrain the patient to perform visual fixation on the fixation target 372prior to clicking the mouse to initiate the presentation of anadditional test pattern, and because it may also be possible toindependently monitor patient fixation by the presentation ofartificially distorted test pattern as disclosed hereinabove andhereinafter.

In accordance with one embodiment of the invention, after a sufficientnumber of test patterns at appropriate locations have been presented tothe patient to adequately map the desired field of vision with a desiredresolution, the test may be terminated. In accordance with anotherembodiment of the invention, the test may further continue by changingthe orientation of the presented test patterns such that a new sequenceof test patterns is presented to the patient which test patterns arevertically oriented segmented straight line.

In screen 420 of FIG. 5F a vertically oriented test pattern 422 isillustrated. Preferably, but not necessarily, the shape, length andnumber of segments of the vertically oriented test pattern 422 may besimilar to the shape, length and number of segments of the horizontallyoriented test patterns previously presented to the patient (such as, forexample, the horizontally oriented test pattern 382 of FIG. 5B). This,however is not mandatory, and the shape, or the length or the number ofsegments of the vertically oriented test patterns may be different thanthose of the horizontally oriented test patterns.

If the patient noticed no difference or distortion in the perceivedpattern (not shown) of the test pattern 422 presented to the patient,the patient may re-fixate on the fixation target 372, and indicatevisual fixation by clicking the mouse 125 to cause the presentation of anew (vertically oriented) test pattern.

FIG. 5G illustrates an exemplary (vertically oriented) test patternpresented to the patient during a part of the test. The test pattern 432is presented in a location of screen 430 as illustrated in FIG. 5G.

FIG. 5H schematically illustrates a screen 440 which is a representationof how the presented screen 430 (of FIG. 5G) may be perceived by thepatient having a retinal lesion while the patient's tested eye isfixated on the fixation target 372. The perceived image perceived by thepatient may be a distorted segmented line 442 (FIG. 5H). In theperceived distorted line 442, the segments 442A, 442B, and 442C areperceived as shifted or distorted, or forming a bulge such that they arenot arranged in a straight line. This perceived distortion may possiblybe due to the presence of the same retinal lesion which caused thedistortion in the perceived image 392 (FIG. 5C) of the presented testpattern 382 of FIG. 5B. The distortion in the perceived image 442 mayhowever also be due to the presence of another different retinal lesion.

After the termination of the presentation of the test pattern 432 (FIG.5G), the patient may mark the location of the perceived distortion asillustrated in screen 450 of FIG. 5I by moving the cursor 373 to pointat the approximate location of the distortion and clicking the mouse 125which stores data representing the location of the observed distortionin the computer system 105, as disclosed hereinabove. Additionalvertical test patterns at different locations may then be presented tothe patient until the mapping of the retina using vertically orientedtest patterns is completed at a desired resolution. Testing of thesecond eye of the patient may then be also performed by covering oroccluding the already tested eye of the patient and repeating the sametesting procedure for the uncovered non-tested eye.

The Use of “Artificial Distortions” in the Flash Test Method

Preferably, in accordance with an embodiment of the invention, it may bepossible to include intentional distortions in the test patternspresented in the flash test method disclosed hereinabove by presentingthe patient with artificially distorted test patterns. The artificiallydistorted patterns may include, inter alia, any of the types ofdistortions included in the artificially distorted test patternsdisclosed hereinabove for the “moving line” test method (for one,non-limiting example of such an artificial distortion see screen 360 ofFIG. 3). Thus, some of the test patterns presented to the patient may beartificially distorted, as disclosed hereinabove. For example, one outof three (approximately 30%) test patterns presented to the patient maybe an artificially distorted pattern. Other different ratios ofartificially distorted to non-distorted test patterns may also be used,as well as tests in which all test patterns include artificialdistortions.

Among the advantages of presenting artificially distorted test patternsis, that this may train the patient in what may be the appearance of aperceived distortion if a retinal lesion is present. This training mayimprove the patient's ability to detect and report such distortions ifsuch a distortion or similar distortions appear in the perceived imagefollowing the presentation of a non-distorted test pattern to thepatient.

Another advantage, as explained hereinabove, may be the possibility toassess the degree of attention of the patient, and the reliability ofthe test results. Thus, if the patient fails to reliably report thepresence and the location of the distortions displayed in theartificially distorted test patterns, this may be used as an indicationof possible lack of attention of the patient, due to fatigue or otherreasons, or this may also be used as an indication that something iswrong with the test presentation or with the test results, or with thepatient's ability to visually perceive the test patterns, in which casethe test results may be ignored (such as, for example, when the test isperformed by the patient alone without the supervision of a trainer orsupervisor). If a trainer or supervisor is present near the patient andsuch a testing non-reliability is reported, for example by anappropriate error message (not shown) appearing on the screen 112 orotherwise, the supervisor or trainer may stop the test (and may cancelthe record of the test results if appropriate) and may try to find andrectify the reasons for the patient's failing to reliably report thepresence and location of the distortions.

For example, the trainer or supervisor may check if the patient's testedeye is positioned at the appropriate distance from the screen 112, or ifthe patient is fatigued or not paying attention to the test patterns ornot properly fixating his vision at the fixation target 373, or thelike. Such problems may be thus rectified and another test may beinitiated if desired.

FIG. 5J illustrates one possible form of an artificially distorted testpattern which may be possibly used in the example of the flash testingmethod illustrated in FIGS. 5A-5I. In screen 460 of FIG. 5J anartificially distorted line 462 is illustrated as presented to thepatient on the screen 112. The segments 462A, 462B and 462C of thepresented line 462 are positioned and oriented such that they are notaligned (or mis-aligned) with the remaining segments of the test pattern462. In other words, while the remaining segments of the test pattern462 are aligned to form a straight line, the segments 462A, 462B and462C form a bulge or curved part or wavy part of the test pattern 462.The test pattern 462 (which may be presented on the screen 112 of thedisplay device 115) is thus an artificially intentionally distorted testpattern. Thus, when the artificially distorted test pattern 462 ispresented to the patient who is visually fixated on the fixation target373, the patient may perceive the distortion as a deviation of thesegments 462A, 462B and 462C from the expected reference pattern of astraight segmented line.

The patient may then proceed to indicate or mark the approximatelocation of the perceived distortion by bringing the cursor 373 to theapproximate location of the perceived distortion and clicking the mouse125 as disclosed in detail hereinabove. For example, the patient mayposition the cursor 373 at the approximate position on the screen 112 atwhich the patient perceived the image of the segment 462B while the testpattern 462 was presented (flashed) on the display device 115, and mayclick on the mouse 125 to input and store the approximate location ofthe perceived distortion in the test pattern 462. The location reportedby the patient may be compared to the known location of the distortionin the presented artificially distorted test pattern 462.

It is noted that when the patient marks the location of the perceiveddistortion, an error or inaccuracy in localization may occur along asingle dimension only (the horizontal dimension for horizontal testpattern, or the vertical dimension for vertical test pattern), since thelocation of the presented test pattern is known to the system.

It is also noted that if the patient detects or observes two or morespatially distinct distortions or abnormalities along the presented testpattern, the patient may mark the approximate location of all suchdetected distortions or visual abnormalities by suitably bringing thecursor 373 to the location at which the additional distortion or visualabnormality was observed and clicking the mouse 125. Thus, the datastored for a test pattern may include the location on the test patternof more than one detected distortion or visual abnormality.

Typically (but not necessarily), about a third (approximately 30%) ofthe test patterns presented to the patient may be artificially distortedtest patterns. The percentage of the artificially distorted test patternout of all the test patterns presented to the patient may however vary,depending, inter alia, on previous knowledge of the test performance ofthe same patient in past tests, or on other considerations. Thus, insome tests, all the test patterns may be artificially distorted.

It is noted that the tests of the present invention may be performedsuch that only a certain percentage of the test pattern include an AD,or, alternatively, the tests may be performed such that all the testpatterns in the test include an AD.

Additionally, the artificially distorted test patterns may be randomlyor pseudo-randomly distributed among the rest of the test patternsduring a test so that the patient cannot predict the time ofpresentation of the artificially distorted test patterns by learning thesequence of presentation of these signals.

It is noted that generally vertically oriented artificially distortedtest patterns (not shown) may also be presented to the patient (the word“generally” refers to the vertical orientation of the majority of thenon-distorted segments which are aligned along an imaginary straightline, even if some of the segments may be horizontally displaced in theregion of the artificial distortion).

Typically, the location of the distorted portion or segments on theartificially distorted test pattern may be randomly or pseudo-randomlychanged or altered in different presentations of artificially distortedtest patterns performed within a test. Such random alteration of thelocation of the artificial distortion along the test pattern isadvantageous because it makes it more difficult for a patient to cheat(either intentionally or non-intentionally) in comparison with asituation in which the distortion is always presented at a fixedlocation on the test pattern.

If the patient fails to reliably identify and report the presence andthe location of the distortion presented in a predetermined percentageof the artificially distorted test patterns which were presented to thepatient in a test, the test results may be ignored or discarded asunreliable. For example, in accordance with one non-limiting exemplaryembodiment of the method of the present invention, if the patient didnot report reliably the presence and the location of the artificialdistortion (or another test pattern modification used in the test) in20% of the total number of artificially distorted test patternspresented within a test, the test results may be ignored or discarded asunreliable.

Thus, in accordance with such an exemplary (non-limiting) testreliability criterion, if in a test the patient was presented with 60test patterns, and 20 test patterns out of the 60 test patterns wereartificially distorted (or otherwise modified) test patterns, thepatient has to reliably report the presence and location of theartificial distortion (or of any other test pattern modification whichwas used in the modified test pattern) in at least four out of thetwenty presented artificially distorted test patterns in order for thetest results to satisfy the reliability criterion.

It is noted that in accordance with the exemplary embodiment of thereliability criterion disclosed hereinabove, it is not enough for thepatient to just identify the presence of the distortion or modificationwhich was artificially introduced in the presented test pattern, but thepatient has to correctly mark the position of the artificial distortion(or other test pattern modification) in the test pattern within aspecified predefined positioning accuracy criterion.

Typically, in accordance with one possible exemplary embodiment of thepresent invention, the position marked by the patient as the position ofthe distortion (or other modification, if used) has to fall within a1.5° cone angle on each side of the center point of the artificialdistortion in to satisfy the position accuracy criterion, but otherdifferent cone angles may also be used.

Reference is now made to FIG. 6 which is a schematic diagram useful inunderstanding an exemplary positioning accuracy criterion which may beused in the eye testing method, in accordance with one exemplaryembodiment of the present invention.

The segmented line 532 schematically represents an artificiallydistorted horizontal line 532 as presented (flashed) on the screen 112to the subject 100. The segment 529 represents the approximated centerof the artificial distortion of the line 532 as presented on the screen112. The tips of the arrows 541, 542, 543, 544 and 545, schematicallyrepresent some possible locations where a subject may potentially markthe position of the approximate the center of the perceived distortion.It is noted that the points clicked on by the subject (which areschematically indicated by the points at the tip of the arrows 541, 542,543, 544 and 545) need not be on the exact line 532 as perceived by thepatient and may be either on or below or above the position on thescreen 112 at which the line 532 was briefly presented. The dashed line519 schematically represents an imaginary vertical line passing throughthe center of the segment 529 and the dashed lines 515 and 517schematically represent two imaginary lines parallel to the verticalline 519 and extending to the end (not shown) of the screen 112. Thedistance S1 between each of the imaginary lines 515 and 517 and theimaginary line 519 is equivalent to a cone angle of 1.5° of the visualfield of the subject (when the subject's eye is positioned 50centimeters from the screen 112).

If the position marked by the subject 100 falls on one of the imaginarylines 515 and 517 or falls anywhere between the two lines 515 and 517,the marked position passes (satisfies) the positioning accuracycriterion and the marked position is deemed to be accurate. If theposition marked by the subject 100 falls on the region on the left sideof the imaginary line 515 or on the screen region on the right of theimaginary line 517, the marked position does not satisfy the positioningaccuracy criterion and the marked position is deemed to be inaccurate.Thus, for example, the marked positions represented by the tip of thearrows 541 and 545 do not satisfy the positioning accuracy criterionwhile the marked positions represented by the tip of the arrows 542, 543and 544 satisfy the positioning accuracy criterion.

It is noted that other different types of positioning accuracy criteriamay also be used. For example the cone angle represented by the distanceS1 may have other values which are smaller or larger than 1.5°.Furthermore, if the test patterns used are slanted lines, otherpositioning accuracy criteria may need to be established and used.

It is further noted that the satisfying of the positioning accuracycriterion may be computed or evaluated by the computer 105 or by anyother suitable computing device, using any suitable computationalalgorithm as is known in the art.

Analysis of Test Results

The results of the tests performed as disclosed hereinabove may need tobe suitably analyzed in order to provide the patient with properinstructions, and possibly his health care provider with a report of thetest results. In the case where the patient has been trained to performthe test at home using a desk-top computer or a portable computer (alaptop computer) or the like, if a possible retinal lesion is detectedin the test, the patient may be preferably provided with an output whichmay instruct the patient to promptly visit his ophtalmologist or an eyeclinic for a thorough eye examination in order to check the existence ofthe suspected lesion. If upon this eye examination a lesion is verified,proper therapeutic treatment may be timely administered to the patient,which may substantially improve patient's prognosis due to earlydetection of the lesion. If no lesion is detected or suspected, thepatient may be informed after the test is finished that the results arenegative (no lesion is suspected).

Theoretically, if a single occurrence of a perceived distortion of atest pattern is reported or marked by the subject after a non-distortedtest pattern is presented to the patient, the patient may be diagnosedas positive and the system may recommend or instruct the patient tovisit an ophtalmologist for further eye examination. Such a simplediagnostic criterion may, however, result in a relatively largepercentage of false positive diagnoses. This is because many patientsmay report a distortion in a certain percentage of the presentednon-distorted test patterns. Thus, such a simple diagnostic criterionmay not be widely applicable to all patients and may possibly be usedonly for a certain sub-population of patients (such as for example invery high risk patients in which it may be decided that a highpercentage of false positive diagnoses is tolerable). It is, howevernoted, that it is possible to use such a single reporting of a perceiveddistortion for diagnosing attested individual as positive provided theempirically determined percentage of false positive results isacceptable in view of the application used.

In accordance with another embodiment of the invention, in testembodiments in which there are multiple presentations of the testpattern the test may result in a positive result if the testedindividual indicates a perceived distortion in a non-distorted positionof a presented test pattern a preselected number of times. For example,the diagnostic algorithm may output a positive result if the testedindividual indicates a perceived distortion in a non-distorted positionof a presented test pattern three or more times within the same test.The number three in this non-limiting example, is the threshold foroutputting a positive test result.

This may have the advantage of reducing the number or the percentage offalse positive results in the test. In accordance with such anembodiment of the test of the present invention, the threshold foroutputting a positive test result may thus vary between a singleoccurrence of a perceived distortion and any desired number higher thanone of such perceived distortions. The choice of the threshold numbermay depend, inter alia, on the number of presentations of the testpattern within a single test, the number of repetitions of presenting atest pattern at the same retinal location, the acceptable percentage offalse positive results, and other practical considerations.

In accordance with one possible embodiment of the test, a positiveresult may be output if the number of presentations of a non-distortedtest pattern in which the patient indicated the presence of a perceiveddistortion is equal to or exceeds the threshold number irrespective ofthe location of projecting of test patterns on the retina.

In accordance with another possible embodiment of the test, a positiveresult may be output if the number of presentations of a non-distortedtest pattern in which the patient indicated the presence of a perceiveddistortion is equal to or exceeds the threshold number and all the testpatterns for which a distortion was indicated were projection the sameretinal location.

For most patients, however, other diagnostic criteria may have to beused for reducing the probability of false positive diagnosis.

In accordance with one possible embodiment of the invention, in order toestablish if one or more visual disturbance was reliably detected, thedata collected and stored in the test is processed as follows.

The data stored for all the non distorted test patterns are checked tosee if any segment or component or portion was marked by the patient onany of the test patterns presented in the test. If such a marked segmentor component or portion is found, the data for other test patterns ischecked for the presence and location of marked segments in otherdifferent test patterns. While the finding of a single marked locationin a single test pattern may be regarded as an indication of a suspectedretinal lesion or retinal abnormality, such a single marked location mayhave been erroneously marked. It is therefore preferred to corroboratesuch a result by checking the data obtained for other different testpatterns to find out if another location was marked on another testpattern. If two locations were indeed marked by the subject in twodifferent test patterns it may be checked or computed if these twolocations satisfy a proximity criterion.

Reference is now made to FIGS. 7A and 7B which are schematic diagramsuseful in understanding exemplary diagnostic criteria which may be usedin some embodiments of the present invention.

It is noted that the locations of the distortions marked and stored inthe computer 105 as disclosed hereinabove may be normalized since theyare all known relative to the fixation target. In other words, acorrection may be computed to compensate for the movement of thefixation target on the screen 112. Therefore, the coordinates of themarked locations may be normalized relative to the fixation target (ifthe fixation target moves on the screen 112 as is the case in the movingline test). In this way all the marked points may be related to eachother for performing the computations of the diagnostic criteria. In thedisclosed exemplary embodiment of flash test, there is no need fornormalization since the fixation point does not change its position onthe screen 112, and therefore the locations (coordinates) of the markedlocations of the distortions or modifications may be used directlywithout normalization. It is however noted, that if an embodiment of theflash test is used in which the position of the fixation target changesduring the test, the coordinates of the positions marked by the testedindividual may be similarly normalized.

Different proximity criteria may be used for different combinations oftest patterns. The computation is performed on pairs of marked locationsin two test patterns. If the pair of marked locations came from testpatterns which are orthogonal to each other (such as for example ahorizontal straight segmented line and a vertical straight segmentedline), the proximity criterion is satisfied if the distance between thetwo marked locations is equal to or smaller than a cone angle of 3°(three degrees) assuming that the subject's eye was at a distance of 50centimeters from the screen 112 during the test.

The point 570 of FIG. 7A schematically represents the position of afirst location marked by the subject in response to the presentation ofa first test pattern. The circle 572 has a radius R which is equivalentto a cone angle of 3° (three degrees) assuming that the subject's eyewas at a distance of 50 centimeters from the screen 112 during the test.If a another point which represents the location marked by the subjecton another test pattern orthogonal to the first test pattern falls on orwithin the circumference of the circle 572, the proximity criterion (forpairs of orthogonal test patterns) is met, indicating the presence of aretinal lesion. If the other point falls outside of the circumference ofthe circle 572, the proximity criterion is not met. For example, eachpoint of the points 576 and 578 meets the proximity criterion withrespect to the point 570, while the point 574 does not meet theproximity criterion with respect to the point 570.

It is noted that if the distance between the tested eye and the screen112 is different than 50 centimeter, the proximity criterion may need tobe changed by changing the value of the radius R.

If the two points being checked come from locations marked on testpatterns that are parallel (for example, two differently locatedstraight segmented lines which are parallel), another proximitycriterion is used.

The point 580 of FIG. 7B schematically represents the position of afirst location marked by the subject in response to the presentation ofa first test pattern. A rectangle 590 surrounding the point 580 has ahorizontal side HS which is equivalent to a cone angle of 4° (fourdegrees) and a vertical side VS which is equivalent to a cone angle of6° (six degrees) assuming that the subject's eye was at a distance of 50centimeters from the screen 112 during the test. The point 580 isdisposed at the geometrical center of the rectangle 590. If anotherpoint which represents the location marked by the subject on anothertest pattern parallel to the first test pattern falls on or within thecircumference of the rectangle 590, the proximity criterion (forparallel test patterns) is met indicating the presence of a retinallesion. If the other point falls outside of the circumference of therectangle 590, the proximity criterion is not met. For example, eachpoint of the points 582, 584, and 576 meets the proximity criterion withrespect to the point 580, while the point 588 does not meet theproximity criterion with respect to the point 580.

It is noted that the proximity criteria disclosed hereinabove wereempirically determined and that many other different types of criteriamay be used, depending, inter alia, on the purpose of the test, theneeded accuracy, the desired level of false positive diagnosis, and theparticular group of patients for which the test needs to be applied.Thus, the proximity criteria indicated above are given by way of exampleonly and other proximity criteria may be applied which are all withinthe scope of the invention.

It is further noted that when the test includes test patterns withartificial distortions, any locations which are marked by the subjectwhich are within approximately 2.83° (2.83 degrees) on each side of thecenter of the artificial distortion are removed from the data prior toperforming the calculations for checking any of the proximity criteriato prevent spurious positive results.

It is, however, noted that if the size and/or shape of the artificialdistortion is changed, a different distance from the center of thedistortion may be used for ignoring data which is assumed to result fromthe presence of the artificial distortion. It is also noted that whenignoring such data as described hereinabove, the same distance may beapplied for all the artificial distortions presented provided that thelongitudinal dimension of all the artificial distortions along the testpattern is identical. The application of this distance criterion may,however, be modified if the longitudinal dimension of the artificialdistortions presented varies for different artificial distortionspresented within the same test, as is disclosed in detail hereinafter.

FIG. 8 is a schematic flow diagram useful in understanding a method forperforming a test session and analyzing the results of the test session,in accordance with one possible embodiment of the present invention.

A test session may include one or more tests and begins by the patientperforming a first test (step 550). The tests may be a moving line testor a flash test but in one session all tests are of the same type. Afterthe first test is completed, the data is analyzed (step 552). Theanalysis may be performed using the proximity criteria as disclosedhereinabove and may result in any of three types of analysis results asfollows:

-   -   1) a positive result is generated if a retinal lesion is found        from the results of the first test by having at least two marked        locations in two separate test patterns which meet the proximity        criteria disclosed hereinabove.    -   2) a negative result is generated if the patient did not mark        any location in any of the test patterns presented in the test.    -   3) a verify result is generated if the patient selected and        marked locations on one or more test patterns presented during        the test, but the marked locations did not meet the proximity        criteria.

If the results of the analysis of step 552 generate a positive result,the session ends with a positive result (step 564) indicating that alesion has been detected, and the session is terminated.

If the results of the analysis of step 552 generate a negative or averify result, a second test is run (step 554). The second test is arepetition of the first test. The results of the second test areanalyzed (step 556) according to the same method as in the analysis ofstep 552 except that the analysis is run on the pooled results of thefirst and the second test.

If the results of the analysis of step 556 generate a positive result,the session ends with a positive result (step 564) indicating that alesion has been detected, and the session is terminated.

If the results of the analysis of step 556 generate a negative result,the session ends in a negative result and is terminated (step 562). Ifthe results of the analysis of step 556 generate a verify result averification test is run (step 558). The verification test may bedifferent than the first test and the second test in that it does notpresent to the patient the full complement of the test patterns whichare normally included in the first and the second test, but presents tothe patient only test patterns which were previously marked by thepatient in the pooled results of the first and the second tests.Additionally, while the first and second tests may include artificiallydistorted test patterns, preferably, the verification test does notinclude artificially distorted test patterns.

After the verification test is performed, an analysis is performed onthe pooled results of the first test, the second test and theverification test (step 560).

If the results of the analysis of step 560 generate a positive result,the session ends with a positive result (step 564) indicating that alesion has been detected, and the session is terminated.

If the results of the analysis of step 560 generate a negative or averify result, the session ends with a negative result (step 562) andthe session terminates.

Experimental Results

Reference is now made to FIG. 9 which is a bar graph representingexperimental results comparing the performance of the standard Amslergrid test with the performance of the eye test of the present invention.

The bar graph of FIG. 9 represents the results of testing performed on108eyes of patients with clinically diagnosed forms of AMD and on agroup of control patients which had a normal retina (the control group).

The test was performed using the flash method as disclosed hereinabove.

The test patterns used were 23 vertical segmented straight lines and 23horizontal straight segmented lines, each line spanning a 14° cone angleat a distance of 50 centimeters of the eye from the screen 112. Thesegments were rectangular white segments on a black background, eachsegment spanning 0.22°×0.22° cone angle. The segments of each line wereseparated from each other by a cone angle of 0.6°.

The results of the control group which included 51 patients clinicallydiagnosed as having normal retinas, are represented in the bar pairlabeled I (normal retina).

A group with 108 patient included four subgroups. The first subgroup(labeled II) included 18 patients clinically diagnosed as having earlyAMD without high-risk characteristics (HRC) as in known in the art.

The second subgroup (labeled III) included 35 patients clinicallydiagnosed as having early AMD with high-risk characteristics (HRC) as inknown in the art.

The third subgroup (labeled IV) included 23 patients clinicallydiagnosed as having late AMD with geographic atrophy (GA) as in known inthe art.

The fourth subgroup (labeled V) included 32 patients clinicallydiagnosed as having choroidal neovascularization (CNV) as in known inthe art.

The results of the MCPT for the subgroups are represented by the hatchedbar of each bar pair and the results of the standard Amsler grid testare represented by the unfilled bar of each bar pair. The height of thebars represents the percent of the patients in each relevant group whichwas diagnosed as positive in the test (Amsler test or MCPT test).

It can be seen that for subgroups II, III, IV, and V the MCPT testresulted in a significantly higher percentage of patients beingpositively diagnosed, as compared to the percentage of the patientdiagnosed positive when the Amsler grid test was applied to the samegroup.

In the normal retina group (the control group I), the differenceobserved between the percentages of individuals showing positivediagnosis in the MCPT and Amsler grid test was not statisticallysignificant.

Testing System Configurations

It is noted that the testing systems and data analysis methods disclosedhereinabove may be implemented in different device and systemconfiguration.

In accordance with one possible configuration of the system, the systemmay be implemented on a computer used at the patient's home. Such acomputer may or may not be connectable to a network as disclosed indetail hereinabove. A software program may be installed on acommercially available desktop computer, or portable computer or anyother suitable type of computer. The computer may be preferablyconnectable to a network for communicating the test results to asuitable server. Such a system may have the advantages of beinginexpensive, simple to operate, and being operable at the patient'shome.

In accordance with another configuration of the test system, the systemmay be meant for use at an eye clinic or at an ophtalmologist's office.Such a system may be implemented on a powerful computer station orworkstation and may also provide the ophtalmologist or other eye expertwith more advanced data analysis and possibly graphical reports of thetest results. Such reports may advantageously provide data about thepossible location of the retinal lesion(s), an indication of the lesionsize or magnitude, and may possibly include a more detailed reportshowing the history of test results of the tested patient.

It will also be understood that the system according to the inventionmay be any suitably programmed computer. Likewise, the inventioncontemplates a computer program being readable by a computer forexecuting the method of the invention. The invention furthercontemplates a machine-readable memory tangibly embodying a program ofinstructions executable by the machine for executing the method of theinvention.

It is noted that while the non-limiting examples of the testing systemdisclosed hereinabove and illustrated in FIG. 1 include a display deviceon the surface of which the various test patterns and the fixationtarget are presented to the subject, other types of systems foradministering the test to the subject may be used which do not include ascreen or surface. For example, in accordance with another embodiment ofthe present invention the test patterns and fixation target(s) may bepresented to the subject by using an optical system (not shown) similarto a scanning laser ophtalmoscope (SLO).

Reference is now made to FIG. 10 which is a schematic diagramillustrating a system including a scanning laser device usable forcarrying out an eye test according to another preferred embodiment ofthe invention.

In the system 600, the images of the test patterns and fixationtarget(s), and possibly the log-on screen(s) may be directly projectedon the retina of an eye 614 of the test subject (not shown) by suitablydirecting a laser beam 612 (schematically represented by the dashed linelabeled 612) through the pupil of the tested eye 614 and by suitablyscanning the laser beam 614 across the retinal surface to form projectedimages of the test patterns and/or fixation target(s) at specifiedlocations on the retinal surface. The system 600 may include a scanninglaser device 602. The scanning laser device 602 may be a scanning laserophtalmoscope (SLO) device as is known in the art, or any other devicecapable of controllably scanning a beam of coherent or non-coherentlight across the retina of an eye. The scanning laser device 602 may besuitably coupled to a controller unit 604 or to a computer (not shown)for controlling the operation of the scanning laser device 602. Thecontroller unit 604 may also be a computer such as a workstation, ormainframe, or laptop computer or a hand held or other portable computingdevice, or a personal computer or any other type of computing deviceknown in the art. The controller unit 604 may be coupled to suitablepointing device(s) 610. The pointing device(s) 610 may be a mouse (notshown), and/or keyboard connected to a computer or may be any othersuitable pointing device or devices as disclosed hereinabove or as knownin the art. The system 600 may also include one or more output unit(s)608, such as, but not limited to, a display, a printer unit, or anyother suitable output device for enabling interaction of a user with thesystem 600 and/or for producing hard copy output of test results or thelike. The output unit(s) 608 may be suitably coupled or connected to thecontroller unit 604.

In operation the system 600 may be used for applying any of the testsdisclosed hereinabove but instead of showing the test pattern, and thefixation targets on a screen 112 of a display device 115, the images ofthe test patterns and the fixation target(s) may be directly projectedonto the retina of the tested eye 614 by the scanning laser device 602by suitably scanning the laser beam 612 on the retina of the eye 614.The laser beam 612 may also be used to project an image of a cursor(similar to the cursor 225 of FIG. 3) directly on the retina of the eye.The movement of such a projected cursor may be controlled by the one ormore of the pointing devices 610, such as but not limited to a mouse(not shown).

Thus, the system 600 may be used to administer to a patient any of thetests disclosed hereinabove (including but not limited to the movingline test and the flash test) and to record and store the responses ofthe patient including but not limited to the marking of parts orportions or segments at which distortions or modifications as disclosedhereinabove were perceived and marked by the patient. The system 600 mayalso process the test results using any of the methods and test criteriadisclosed hereinabove to produce a positive or negative diagnosis. Thesystem 600 may also be suitably connected to a communication network(such as, but not limited to the communication network 130 of FIG. 1)and may communicate with other devices or computers, or the like, overthe communication network.

It is noted that the laser scanning device 602 may be replaced orsubstituted with other scanning devices (not shown) known in the artwhich are capable of directing a narrow light beam having a suitablynarrow beam cross-sectional area onto an eye and scanning the beamcontrollably across the retina. The light beam need not be a laser beambut may be any beam of non-coherent light which may be suitably scannedacross a retina with sufficient speed and resolution.

It is noted that the construction and operation of laser scanningophtalmoscopy devices are well known in the art, are not the subjectmatter of the present invention and are therefore not described indetail herein.

Assessment of Disease Progression in AMD

While the testing procedure disclosed hereinabove and graphicallyillustrated in FIGS. 4A-4J may produce data which may be analyzed todetermine the presence of retinal abnormalities (such as, but notlimited to, AMD related retinal lesions or diabetes related retinallesions, or the like), and to determine whether a patient tests positiveor negative for the presence of retinal lesions, it may also bedesirable to determine the degree of severity of the detected retinallesion or lesions and to determine the stage or progression of diseasein the tested patient or subject.

AMD patients may generally be clinically divided into groups such aspatients having early AMD without high-risk characteristics (HRC),patients having early AMD with HRC, patients having late AMD withgeographic atrophy (GA), and patients having advanced AMD with choroidalneovascularization (CNV). It may be desirable to classify a patient asbelonging to a patient group, such as one of the above indicated groupswithout having to resort to a lengthy and expensive retinal examinationby an ophtalmologist.

As disclosed hereinabove, in a patient having a retinal lesion, when thepatient is presented with a non-distorted test pattern at a firstlocation on the screen 112 of the display device 115, which causes theimage of the test pattern to be projected on the retina such that partof the projected image of the test pattern falls on the lesioned regionof the retina, the patient may observe a distortion or abnormalappearance of part of the perceived image of the test pattern. This typeof observed distortion or other abnormal or modified appearance orchange in the perceived image of the test pattern is referred to as apathology related observed distortion (PROD) hereinafter.

While performing the visual tests disclosed hereinabove, which includedthe use of artificially distorted test patterns for testing the patientsreliability in perceiving and/or reporting these artificially introduceddistortions, the inventors of the present invention have noticed that ifan artificially distorted test pattern is presented at a location on thescreen 112 such that part of the projected image of the test patternfalls on a lesioned region of the retina, the patient may respond to thepresentation of the test pattern in one of four different types ofresponses.

In the first type of possible response, the patient may perceive andmark two distortions at two locations of the perceived image of theartificially distorted test pattern. One perceived distortion may beassociated with the presence of the retinal lesion and is thereforedefined as a PROD and the other perceived distortion may be associatedwith the distortion which was artificially introduced into the displayedartificially distorted test pattern. The latter type of observeddistortion is referred to as an artificially introduced observeddistortion (AIOD) hereinafter. This first response type is referred toas a “B type” response hereinafter, to indicate that the patientreported both the PROD and the AIOD.

In a second type of possible response, the patient may perceive and markonly the distortion associated with the presence of the retinal lesion(only the PROD). This second response type is referred to as a “P type”response hereinafter, to indicate that the patient reported only thePROD.

In a third type of possible response, the patient may perceive and markonly a distortion associated with the presence of the distortion whichwas artificially introduced into the presented test pattern (only anAIOD). This third response type is referred to as an “A type” responsehereinafter, to indicate that the patient reported only the AIOD.

In the fourth type of possible response, the patient may not observe ormark any distortion at all. This fourth response type is referred to asan “N type” response hereinafter, to indicate that the patient did notreport any observed distortion.

Reference is now made to FIG. 11 which is a diagram schematicallyillustrating four different possible response types of the same patientwhen the patient is presented with a test pattern including anartificial distortion, such that part of the projected image of the testpattern falls on a retinal lesion in the patient's retina.

The distorted segmented lines 615A, 615B, 615C, and 615D schematicallyrepresent a test pattern presented to the patient as disclosed in detailhereinabove (by presentation on a display device, such as for examplethe screen 112 disclosed hereinabove, or by direct retinal projectionsuch as for example by using the system 600 disclosed hereinabove). Itis noted that the distorted segmented lines 615A, 615B, 615C, and 615Dschematically represent the test pattern as presented to the patient(and not the patterns as observed by the patient).

The artificial distortions 617A, 617B, 617C, and 617C comprise displacedsegments of the segmented lines 615A, 615B, 615C, and 615D,respectively. The rectangular boxes 619, 620, 621, and 622,schematically represent regions of the test pattern in which the patientplaced a mark in the various different response types. It is noted thatthe boxes 619, 620, 621, and 622 do not indicate the precise position inwhich the patient marked an observed distortion but rather schematicallyrepresent the approximate position at which the patient observed adistortion.

The segmented line 615A and the rectangular boxes 619 and 620superimposed thereon schematically represent a non limiting example of aresponse in which the patient reports at least two observed distortionsby marking at least two different regions on the test pattern inresponse to the presentation of a test pattern including an AD 617A. Thebox 619 schematically represents the region in which the patientobserved a distortion due to a retinal lesion (a PROD), and the box 620schematically represents the region in which the patient observed adistortion due to the artificial distortion 617A (an AIOD). It is notedthat while this non-limiting schematic example shown illustrates a casein which the patient marked only two positions in response to thepresentation of the test pattern 615A (one marked position correspondingto an AIOD and the second marked position corresponding to a PROD), inother possible responses the patient may mark more than two positions.For example, the patient may mark one position in the region of theartificial distortion 617A and two or more positions in other regions(not shown in FIG. 11) of the test pattern 615A.

The segmented line 615B and the rectangular box 621 superimposed thereonschematically represent a non-limiting example of a response in whichthe patient reports one or more observed distortions by marking one ormore positions on the display screen, in response to the presentation ofa test pattern 615B including an AD 617B, as disclosed in detailhereinabove. The box 621 schematically represents the region in whichthe patient observed a distortion due to the retinal lesion in thetested eye. In this type of response the patient did not report anobserved distortion in the region of the artificial distortion 617B.

The segmented line 615C and the rectangular box 622 superimposed thereonschematically represent a non-limiting example of a response in whichthe patient reports a single observed distortion by marking one positionon the display. The box 622 schematically represents the region in whichthe patient observed a distortion due to the artificial distortion 617C.In this type of response the patient does not observe (and thereforedoes not mark) a distortion due to the presence of the retinal lesion.

The segmented line 615D having no boxes superimposed thereonschematically represents a response in which the patient did not markany position on the display, in response to the presentation of the testpattern because no distortion was observed (and therefore no distortionwas marked) by the patient neither in the region of the AD 617Dpresented in the test pattern 615D nor in the region of the retinallesion.

It is noted that the response types illustrated in FIG. 11 are schematicand are given by way of example only, and that the type of response of apatient to the presentation of a test pattern may depend, inter alia, onthe individual patient being tested, the shape and type of the presentedtest pattern, the actual size and shape of the artificial distortionintroduced into the test pattern, and the type and severity of theretinal lesion in the retina of the tested eye.

The inventors of the present invention have found that when patients arepresented with test patterns including artificially introduceddistortions such that part of the projected image of the test patternfalls on a lesioned region of the retina, there is a correlation betweenthe retinal lesion type of the patient (i.e. the severity of the lesion)and the type of patient response exhibited. Moreover, the type ofresponse also depended on the size or magnitude of the distortionartificially introduced into the test patterns presented to the patient.

By varying the magnitude of the artificial distortion introduced intothe test patterns presented to patients in clinical experiments it wasunexpectedly found that for a particular retinal lesion, as theartificially introduced distortion in the presented test pattern becomeslarger in magnitude, there is a higher probability that the patient maypreferentially observe and report the artificially introduced distortionwhile not observing and reporting a distortion due to the presence ofthe retinal lesion.

Thus, as empirically and unexpectedly found by the inventors of thepresent invention, when patients are presented with test patternsincluding artificially introduced distortions such that part of theprojected image of the artificially distorted test pattern falls on alesioned region of the retina, the probability that a patient willrespond to the presentation of the artificially distorted test patternwith the above described third type of response (observing and reportingonly the AIOD) increases as the magnitude of the distortion increases.

While the exact psychophysical basis for this phenomenon is not yetclear, it may appear as if the PROD and the AIOD “compete” for patient'sattention and that there is a higher probability that a distortion whichis larger or more noticeable or more prominent may be preferentiallynoticed and reported by the patient, and that there may be is a smallerprobability that the smaller or less noticeable or less prominentdistortion will be noticed and reported.

The inventors of the present invention have thus noticed that bypresenting a patient with test patterns having artificially introduceddistortions of various sizes, or amplitudes, or magnitudes (gradeddistortions) which are presented to the patient such that they fall onthe lesioned retinal region and by recording and analyzing the responsesof the patient it may be possible to assess the severity of thepatient's lesion or to classify the patient as belonging to a particularclass of clinically defined disease progression state. For example, inthe case of tested AMD patients it may be possible to classify thetested patients into groups representing different stages of AMD, as isdisclosed in detail hereinafter.

Results of “Competition” Experiments

The competition experiments were performed using artificially distortedtest patterns which were displayed to the patients on the display screenof a laptop computer. The Laptop personal computer used was a DellLatitude laptop computer model C-600, having a 14.1 inch TFT colorscreen, but any other suitable computer or display may also be used.

It is noted that all the angular dimensions disclosed hereinbelow aregiven as cone angles of the visual field of the subject (when thesubject's eye is positioned 50 centimeters from the screen of thedisplay device, such as the display of laptop computer used for thetest). Each of the test patterns displayed on the screen included 27square segments arranged as a segmented line, the segments were whitesegments presented on a black background. Each square segment had thedimensions of 0.26° by 0.26° (cone angles, when observed at a distanceof 50 centimeters from the patient's tested eye as disclosedhereinabove).

In the non-distorted (flat) linear test patterns (not shown), all thesegments were linearly arranged and the distance separating the adjacentends of two adjacent segments was 0.22°. The distance between thecenters of two adjacent segments is 0.52°.

In the exemplary artificially distorted test patterns used in thecompetition experiment, three segments out of the twenty seven squaresegments of the test pattern are displaced such that they are notlinearly arranged relative to the other remaining segments. Theremaining twenty four segments are linearly arranged such that theircenters all lie on a straight line (see, for example, imaginary line 660of FIG. 12 below).

Reference is now made to FIG. 12 which is a schematic diagramillustrating in detail part of a schematic artificially distorted testpattern used in the competition experiments performed in accordance withan embodiment of the present invention.

In FIG. 12, a part of an artificially distorted test pattern 630 isillustrated. Only ten segments 632, 634, 636, 638, 640, 642, 644, 646,648, and 650 of the twenty seven segments of the test pattern 630 areshown.

The segments 632, 634, 636, 638, 646, 648, and 650 are arranged suchthat their centers 632C, 634C, 636C, 638C, 646C, 648C, and 650C,respectively are all disposed along a straight line 660, while thesegments 640, 642 and 644 are disposed such that their centers 640C,642C and 644C, respectively, are offset from the line 660 (it is notedthat the line 660 is an imaginary line given only for the purpose ofillustrating the arrangement of the various segments of the test pattern630, the line 660 does not form a part of the test pattern 630 and isnot shown to the patient). The seventeen segments included in the testpattern 630 and not shown in FIG. 12 (for the sake of clarity ofillustration) may be disposed on the straight line 660 adjacent to thesegment 632, or adjacent to the segment 650. Alternatively some of theremaining seventeen segments which are not shown in FIG. 12 may bedisposed on the straight line 660 adjacent to the segment 632 and therest of the remaining seventeen segments may be disposed on the straightline 660 adjacent to the segment 650.

The left and the right sides of each of the twenty seven segmentsincluded in the test pattern 630 are preferably oriented such that theyare perpendicular to the line 660 (it may, however, also be possible touse other orientations).

The distance D4 between adjacent segments (represented by the doubleheaded arrows D4) is 0.22° and the side D5 of all the square segments ofthe test pattern 630 is 0.26° (as indicated above, the values of D4 andD5 represent cone angles, when observed at a distance of 50 centimetersfrom the patient's tested eye as disclosed hereinabove).

The distorted part of the exemplary test pattern 630 comprises thesegments 640, 642, and 644. The centers 640C, 642C and 644C of thesegments 640, 642 and 644, respectively, are disposed on an (imaginary)half ellipse curve 662 (schematically represented by the dotted linelabeled 662). It is noted that the half ellipse curve 662, and thecenter points 632C, 634C, 636C, 638C, 640C, 642C, 644C, 646C, 648C, 650Care shown in FIG. 12 for explanatory and illustrative purposes only, anddo not appear in the test patterns shown to the patients.

The distance H between the center point 642C of the segment 642 (thecentral segment of the three segments 640, 642 and 644 forming theartificial distortion) and the straight line 660 is defined as theheight of the artificial distortion. The distance H comprises half ofthe minor axis of an ellipse (not shown in its entirety) which includesthe half ellipse curve 662. The distance MA is the major axis of such anellipse.

For the exemplary test pattern 630 partially illustrated in FIG. 12, thecomputer program which generates the test patterns for display on thescreen 112 may compute the positions of the segments of the test patternby using the above indicated segment dimensions (0.26° by 0.26°) andsegment spacing (0.22°) to determine the horizontal coordinate of thecenter point 642C (defined as the position of the center point 642Calong the horizontal axis labeled X), and the vertical coordinate of thecenter point 642C (defined as the position of the center point 642Calong the vertical axis labeled Y). The computer program may thencompute the vertical coordinates of the center points 640C, and 644C asdisposed on the computed half ellipse curve 662. The horizontalcoordinates of the center points 640C, and 644C may be computed from thecomputed horizontal coordinate of the center point 642C and from theknown values of D5 and D4.

Thus, for artificial distortions having different values of H, theimaginary half ellipse curves may be of different sizes.

It is noted that while in the exemplary test pattern 630 of FIG. 12 Themajor axis MA of the ellipse which includes the half ellipse curve 662starts at the center point 638C of the segment 638 and ends at thecenter point 646C of the segment 646, this need not be the case forartificial distortions having different values of the distortion heightsH. In other test patterns (not shown) the computed half ellipse curve(not shown) may intersect the straight line 660 at points which aredifferent than the center points 638C and 646C. The exact points ofintersection of the (imaginary) half ellipse curve and the line 660 maydepend on the values of D4, D5, and H. For example, in accordance withone non-limiting example the computed half ellipse curve (not shown) mayintersect the straight line 660 at a first point (not shown) locatedbetween the center points 636C and 638C and at a second point locatedbetween the center points 646C and 648C.

It is noted that in EXPERIMENT 1 and EXPERIMENT 2 detailed below, thecomputations were rounded to the nearest pixel value to accommodate forthe finite pixel size and resolution on the TFT screen of the laptopcomputer used in the test.

The computer program used for calculating the positions of the varioussegments of the test patterns (such as but not limited to the testpattern 630 partially illustrated in FIG. 12), computed the positions ofthe segments 640, 642, and 644 included in an AD having a height H byusing the equation for an elliptical curve as is known in the art andthe known values of D4, and D5. Such a computation is well known in theart and may be implemented using many computational methods or programcode all of which are known in the art and are therefore not describedin detail hereinafter.

Competition Study Details

The competition study included two different experiments (EXPERIMENT 1and EXPERIMENT 2 disclosed hereinbelow). Each experiment was performedby testing different patient groups. In both experiments, each testedpatient was presented with test patterns using the flash methoddisclosed hereinabove with a test pattern presentation duration of 160milliseconds.

The dimensions are given as cone angles wherein each degree represents300 micron over the retina. If the subject is 50 cm from the displayscreen of the computer, each degree is equivalent to a length of 0.88centimeter on the display screen.

Some of the test patterns were linear (flat) test patterns as disclosedhereinabove, and did not include an artificial distortion. Most of thetest patterns included a single artificial distortion.

Experiment 1

In this experiment two groups were tested. The first group included 28subjects all clinically diagnosed to have normal retinas (normal group).The second group included 32 subjects clinically diagnosed to have AMDwith high risk characteristics (AMD with HRC group). All subjects(ranging in age between 50-90 years old) were given a complete eyeexamination by a retina specialist prior to performing the tests for theexperiment. After the diagnosis was recorded by the retina specialisteach of the patients was tested using an MCPT adapted for the experimentas disclosed hereinafter.

The artificial distortions presented were selected from artificialdistortions (AD) having a height of 0.19°, 0.22° as disclosedhereinabove. Each test pattern had a dimension of approximately 14°.Half of the test patterns presented to each patient, were generallyhorizontally oriented and the other half were generally verticallyoriented, as disclosed hereinabove. Altogether, the test patterns wereadapted to map a 14°×14° grid on the macula with a 1° resolution. Thefovea of the tested eye was at the center of the mapped region. Thesequence of presentation of the horizontal and vertical test patternswithin a single test was randomly selected. The sequence of presentingsignals with an AD and without an AD was also randomized. The sequenceof presentation of the test patterns having different heights (heightsof 0.19°, 0.22°) was also randomized.

Each eye was tested by presenting test patterns at thirty differentlocations on the display of the laptop computer. Fifteen locations werehorizontally oriented on the display of the laptop computer and fifteenlocations were vertically oriented on the display of the laptopcomputer. At each of the thirty different locations on the display ofthe laptop computer there were five randomized presentations of the testpatterns, one presentation of a test pattern with no AD (a flat testpattern), two presentations of a test pattern including an AD with aheight of 0.19°, and two presentations of a test pattern including an ADwith a height of 0.22°. Altogether, each test included 150 presentationsof test patterns to the tested patient's eye.

In the pair of test pattern presentations including an AD with a heightof 0.19°, the position within the test pattern of the three segmentsforming the AD was randomly selected, but the minimal distance betweenthe positions of the AD in the two presentations was 5° (In other words,if the test patterns presented at each of the two presentations were tobe superimposed on each other, the distance between the center points ofthe central segments of each of the ADs would be equal to or larger than5° ).

Similarly, in the pair of test pattern presentations including an ADwith a height of 0.22°, the position within the test pattern of thethree segments forming the AD was randomly selected, but the minimaldistance between the positions of the AD in the two presentations was5°.

It is noted that while the random distribution of the positions of theartificial distortions and the 5° distance ensures adequate distributionof the positions, other methods for setting the positions of theartificial distortions in the test patterns may also be used. Forexample, in other experiments, a look up table (LUT) stored in thememory of the laptop computer or other computer of the computer system105 was used. The LUT included a set of positions selected to generate arelatively uniform distribution of the artificial distortion's positionin the test patterns presented within a test.

The distribution of the positions were sequentially read from the LUTand used by the system to determine the position of the AD within thetest patterns. In accordance with other embodiments of the presentinvention, satisfactory results may thus be obtained using such a LUT ora random number generator, or a pseudorandom generator, or any otheralgorithm adapted for generating randomly or non-randomly distributedpositions of the artificial distortions, as long as the sequence ofpositions cannot be remembered or otherwise memorized or predicted bythe patient or by the individual being tested.

The patients were asked to mark the positions at which a distortion wasobserved, by using a mouse connected to the Laptop computer as disclosedin detail hereinabove for the flash test. All the test data were storedin the laptop computer for further processing and analysis, including,inter alia, all the settings and parameters of the presented testpatterns, the location and height of the AD in the artificiallydistorted test patterns, the sequence of presentation of the testpatterns, and the patients responses to each test pattern presentations.

The results were then processed as follows:

The percentage of marking “flat” test patterns by the patient P_(F) wascomputed according to the equation P_(F)=100 N_(M)/P_(FT), wherein N_(M)is the total number of test pattern presentations in which the patientmarked the presence of one or more observed distortions when presentedwith a test pattern having no AD (a flat test pattern), and P_(FT) isthe total number of test patterns having no AD (“flat” test patterns)which were presented to the patient in the test.

In the exemplary, non-limiting, tests performed in EXPERIMENT 1, thetotal number of presentations of such flat test patterns to a patient ina single test of EXPERIMENT 1 is thirty presentations (P_(FT)=30).

The computer further analyzed the position of the markings by thepatient in response to the presentation of test patterns having an AD,and classified the responses into different types.

The computer analyzes the patient responses to detect two differentpatient response types. The first patient response type is a response inwhich the patient marked one or more positions in response to thepresentation of a test pattern including an AD, and in which all of thepositions marked by the patient were defined as being due to thepresence of a retinal lesion by applying the criteria disclosedhereinafter and illustrated in FIGS. 13 and 14. This type of patientresponse is defined as a P type response hereinafter.

The second patient response type is a response in which the patientmarked at least two positions in response to the presentation of a testpattern including an AD, and in which at least one of the positionsmarked by the patient was defined as being due to the presence of aretinal lesion, and at least one of the positions was defined as beingdue to the artificial distortion present in the test pattern, whereinthe definitions were made by applying the criteria disclosed hereinafterand illustrated in FIGS. 13 and 14. This type of patient response isdefined as a B type response hereinafter.

In the first type of patient response, if all the positions marked bythe patient in response to the presentation of a test pattern includingan AD are at a distance equal to or greater than 2.83° from the positionof the center of the AD, the markings are considered to represent a PRODindicating that the patient observed distortion(s) due to the presenceof a real retinal lesion (or lesions) or abnormality, and the responseis identified and recorded as a P type response.

In the second type of patient response there are at least two positionsmarked by the patient. At least a first position marked by the patientin response to the presentation of a test pattern including an AD is ata distance smaller than 2.83° from the position of the center of the AD.This marking is considered to be due to an AIOD (assuming that thedistortion marked by the patient is due to the AD). Additionally, atleast a second position marked by the patient in response to thepresentation of the test pattern is at a distance equal to or greaterthan 2.83° from the position of the center of the AD. This second markedposition is considered to be due to a PROD (assuming that the distortionmarked by the patient is due to a retinal lesion). Such a response isidentified and recorded as a B type response.

Reference is now made to FIGS. 13 and 14 which are schematic diagramsillustrating in detail the criterion for determining if a positionmarked by the patient is due to a PROD indicating the presence of aretinal lesion or due to an AIOD indicating the observation of anartificial distortion, in accordance with one embodiment of the presentinvention.

FIG. 13 illustrates part of a horizontal artificially distorted testpattern 730. The test pattern 730 includes square segments 732. Thesegments 732 are arranged such that their centers (not shown) aredisposed on an imaginary straight line 760 (the imaginary line 760 isnot part of the test pattern 730, is not shown to the patient, and isshown solely for illustrative purposes to indicate the arrangement ofthe segments included in the test pattern 730). The test pattern 730includes additional segments which are not shown for the sake of clarityof illustration. The test pattern 730 is artificially distorted asdisclosed hereinabove. The test pattern 730 includes segments 740, 742,and 744. The centers of the segments 740, 742 and 744 are offset fromthe imaginary line 760.

The dashed line 753 which starts at the center 742C of the segment 742is perpendicular to the line 760, and intersects the line 760 at thepoint P_(C). The point 750 schematically represents a position marked bythe patient (on the display on which the test pattern 730 is presented)in response to the presentation of the test pattern 730. The dashed line755 which starts at the point 750 is perpendicular to the line 760, andintersects the line 760 at the point P_(M).

The double headed arrow labeled D6, represents the distance D6 betweenthe points P_(C) and P_(M) along the line 760. If the distance D6 isequal to or greater than 2.83° (expressed as the cone angle at adistance of 50 centimeters of the tested eye from the display screen onwhich the test pattern 730 is displayed), the position of the markedpoint 750 is defined as being due to a PROD. If the distance D6 issmaller than 2.83°, the position of the marked point 750 is defined asbeing due to an AIOD.

FIG. 14 illustrates part of a horizontal artificially distorted testpattern 830. The test pattern 830 includes square segments 832. Thesegments 832 are arranged such that their centers (not shown) aredisposed on an imaginary straight line 860 (the imaginary line 860 isnot part of the test pattern 830, is not shown to the patient, and isshown solely for illustrative purposes to indicate the arrangement ofthe segments included in the test pattern 830).

The test pattern 830 includes additional segments which are not shownfor the sake of clarity of illustration. The test pattern 830 isartificially distorted as disclosed hereinabove. The test pattern 830includes segments 840, 842, and 844. The centers of the segments 840,842 and 844 are offset from the imaginary line 860.

The dashed line 853 which starts at the center 842C of the segment 842is perpendicular to the line 860, and intersects the line 860 at thepoint P_(C1). The point 850 schematically represents a position markedby the patient (on the display on which the test pattern 830 ispresented) in response to the presentation of the test pattern 830. Thedashed line 855 which starts at the point 850 is perpendicular to theline 860, and intersects the line 860 at the point P_(M1).

The double headed arrow labeled D7, represents the distance D7 betweenthe points P_(C1) and P_(M1) along the line 860. If the distance D7 isequal to or greater than 2.83° (expressed as the cone angle at adistance of 50 centimeters of the tested eye from the display screen onwhich the test pattern 830 is displayed), the position of the markedpoint 850 is defined as being due to a PROD. If the distance D7 issmaller than 2.83°, the position of the marked point 850 is defined asbeing due to an AIOD.

Using the above disclosed exemplary (non-limiting) criteria, a patient'sresponse to the presentation of a test pattern including an AD in whichat least one marked position was defined as being due to a PROD, isrecorded as a P type response, and a patient's response to thepresentation of a test pattern including an AD in which at least onemarked position was defined as being due to a PROD and at least oneother marked position is defined as being due to an AIOD, is recorded asa B type response.

It is noted that the criteria illustrated in FIGS. 13 and 14 forclassification patient responses as B type or P type responses, aregeneral criteria which may be applied to all the specific positions ofthe artificial distortion within a test pattern, and to the differentpossible positions which may be marked by the patient in response to thepresentation of a specific test pattern including an AD at a particularposition. These criteria may be applied to responses presented atvarious different locations on the display device, as disclosed indetail hereinabove, and test patterns having ADs with different heights

It is further noted, that while the criteria disclosed hereinabove fordistinguishing between a marked position due to a PROD and a markedposition due to an AIOD are schematically illustrated for an example(FIG. 13) in which the segments 740, 742, and 744, included in theartificial distortion, are offset above the line 760 (such an AD isdefined as an upward curving AD hereinafter), the same criteria may alsobe applied to responses generated by test patterns (not shown) having anartificial distortion in which the segments are offset below the line760 (such an AD is defined as a downward curving AD hereinafter).

Similarly, the criteria disclosed hereinabove may be similarly appliedfor responses to test patterns such as the exemplary test pattern 830 ofFIG. 14 including the segments 840, 842, and 844 of the test pattern 830of FIG. 14 in which the segments 840, 842, and 844 of the AD are offsetto the left of the line 860 (such an AD is defined as a left curving ADhereinafter) and to test patterns (not shown) having an artificialdistortion with segments which are offset to the right of the line 860(such an AD is defined as a right curving AD hereinafter).

In all of the presentations of all the test patterns including an AD ofEXPERIMENT 1, the direction of curvature of the artificial distortionwas randomized. Thus, for horizontal test patterns including an AD theprobability that the AD in the presented test pattern is an upwardcurving AD was equal to the probability that the AD is a downwardcurving AD (and both of these probabilities were equal to 0.5).Similarly, for vertical test patterns including an AD the probabilitythat the AD in the presented test pattern is a right curving AD wasequal to the probability that the AD is a left curving AD (and both ofthese probabilities were equal to 0.5).

It is, however, noted, that the direction of the curvature of the ADneed not be randomized in the artificially distorted test patterns whichare presented to a patient within a test. Moreover, it wasexperimentally discovered, in later experiments, that the direction ofcurvature of the distortions observed by patients in response to thepresentation of linear (distorted or non-distorted) test patterns,depends on the direction of movement of the test pattern (in tests usingthe “moving pattern” method disclosed hereinabove), or on the directionof the presented test pattern relative to the fixation target (in testsusing the flash method disclosed hereinabove).

Typically, the PROD observed by the patients was reported to be curvedin the same direction of “movement” of the test pattern (in tests usingthe moving pattern method), and in the direction pointing from thefixation point toward the flashed test pattern (in tests using the flashmethod). In other words, the distorted part of the test pattern asobserved by the patient seemed to be offset (protruding) from the testpattern in the direction of the “movement” of the test pattern (in testsusing the moving pattern method), and in the direction pointing from thefixation point toward the flashed test pattern target (in tests usingthe flash method).

Thus, in accordance with another embodiment of the invention, it mayalso be possible to use in the tests ADs in which the distorted part ofthe test pattern (the AD) presented to the patient is offset(protruding) from the test pattern in the direction of the “movement” ofthe test pattern (in tests using the moving pattern method), and in thedirection pointing from the fixation point toward the flashed testpattern target (in tests using the flash method).

Furthermore, in accordance with yet another embodiment of the invention,it may also be possible to use in the tests ADs in which the distortedpart of the test pattern (the AD) presented to the patient is offset(protruding) from the test pattern in a direction opposite to the“movement” of the test pattern (in tests using the moving patternmethod), or opposite to the direction pointing from the fixation pointtoward the flashed test pattern target (in tests using the flashmethod).

After determining the response types for all of the patient's responsesevoked by the presentation of test patterns including an AD, thecomputer further calculates the following parameters. For all of thetest patterns including an AD with the same height, the computercomputes the values R_(H), and B_(H), wherein R_(H) is the percentage ofresponses classified as P type responses out of the total number of testpatterns including an AD with a height H which were presented to thepatient, and wherein B_(H) is the percentage of responses classified asB type responses out of the total number of test patterns including anAD with a height H which were presented to the patient.

For example, if the patient was presented with 60 test patterns havingan artificial distortion with a height H=0.22° (represented as degreesof the cone angle for a distance of 50 centimeters of the tested eyefrom the display on which the test patterns are presented), and 6responses out of all the patient's responses to the presentation ofthese 60 test patterns were classified as P type responses, thenR_(0.22)=10%. For the same patient presented with the above indicated 60test patterns having an artificial distortion with a height H=0.22°, ifthree responses out of all the patient's responses to the presentationof these 60 test patterns were classified as B type responses, thenB_(0.22)=5%.

The computer then further calculated the value of the competition gradeC_(H) for an artificial distortion having a height H, whereinC_(H)=R_(H)+B_(H).

For example, for the above exemplary test of the same patient for whichR_(0.22)=10% and B_(0.22)=5%, the value of C_(0.22) isC_(0.22)=10%+5%=15%. Thus, for this particular test of the aboveexemplary (hypothetical) patient, the competition grade for anartificial distortion having a height of 0.22°, is 15 percent.

After performing various different empirical calculations based on theanalysis of results of the patients tested in EXPERIMENT 1, thefollowing criteria were selected for determining if the patient belongsto the group with normal retina, or belongs to the group having AMD withHRC, based on the results of the test patterns having ADs with a heightof 0.19° (it is noted that the data from the results of the testpatterns having ADs with a height of 0.22° were not used forestablishing these criteria):

A patient belongs to the group with high risk characteristics AMD (AMDwith HRC group) if at least one of the following two conditions issatisfied:

-   -   1) P_(F)>10%    -   2) C_(0.19)>7%    -   wherein P_(F) and C_(0.19), are as defined in detail        hereinabove.

If none of the above two criteria is satisfied, the patient belongs tothe group having normal retinas (normal group).

When these classification criteria are applied to the test results ofall the patients tested in EXPERIMENT 1, the results were as indicatedin TABLE 1 below. TABLE 1 Patients Patients ophtalmologicallyophtalmologically diagnosed as diagnosed as having having Normal AMDwith HRC retinas Total Patients which 28 2 30 satisfy at least one ofthe conditions: P_(F) > 10% C_(0.19) > 7% Patients which 4 26 30 do notsatisfy any of the conditions: P_(F) > 10% C_(0.19) > 7% Total 32 28 60Calculated sensitivity 87.5%Calculated specificity 93%P < 0.001

Experiment 2

In this experiment, two groups were tested. The first group included 43subjects clinically diagnosed to have AMD with high risk characteristics(AMD with HRC group). The second group included 20 subjects clinicallydiagnosed to have CNV. All subjects (in the age range of 50-90 yearsold) were given a complete eye examination by a retina specialist priorto performing the tests for the experiment. After the diagnosis wasrecorded by the retina specialist each of the patient was tested usingan MCPT adapted for the experiment as disclosed hereinafter.

The artificial distortions presented were selected from artificialdistortions (AD) having a height of 0.19°, 0.22°, and 0.28° as disclosedhereinabove. Each test pattern had a dimension of approximately 14°.Half of the test patterns presented to each patient, were generallyhorizontally oriented and the other half were generally verticallyoriented, as disclosed hereinabove. Altogether, the test patterns wereadapted to map a 14°×14° grid on the macula with a 1° resolution. Thefovea of the tested eye was at the center of the mapped region. Thesequence of presentation of the horizontal and vertical test patternswithin a single test was randomly selected. The sequence of presentingsignals with an AD and without an AD was also randomized. The sequenceof presentation of the test patterns having different heights (selectedfrom heights of 0.19°, 0.22°, and 0.28°) was also randomized, asdisclosed hereinafter.

In all of the presentations of all the test patterns including an AD ofEXPERIMENT 2, the direction of curvature of the artificial distortionwas randomized. Thus, for horizontal test patterns including an AD theprobability that the AD in the presented test pattern is an upwardcurving AD was equal to the probability that the AD is a downwardcurving AD (and both of these probabilities were equal to 0.5).Similarly, for vertical test patterns including an AD the probabilitythat the AD in the presented test pattern is a right curving AD wasequal to the probability that the AD is a left curving AD (and both ofthese probabilities were equal to 0.5).

Each eye was tested by presenting test patterns at thirty differentlocations on the display of the laptop computer. Fifteen locations werehorizontally oriented on the display of the laptop computer and fifteenlocations were vertically oriented on the display of the laptopcomputer. At each of the thirty different locations on the display ofthe laptop computer there were three (3) randomized presentations of thetest patterns, one presentation of a test pattern with no AD (a flattest pattern), each of the two other presentations of a test pattern atthe location included an AD. Altogether, each test included 90presentations of test patterns to the tested patient's eye.

The height of the AD in each of these two remaining presentations wasrandomly selected from the heights 0.19°, 0.22°, and 0.28° withoutrepetition (without repetition means herein that the two ADs presentedat the same location were always of different heights). It is noted thatsince only two (out of three possible) different heights of AD were usedin the test patterns presented at the same location and orientation, thedata for each specific location and orientation of a test pattern didnot include all possible AD heights.

In the two test pattern presentations including an AD, the positionwithin the test pattern of the three segments forming the AD wasrandomly selected, but the minimal distance between the positions of theAD in the two presentations was 5°, as explained in detail forEXPERIMENT 1 hereinabove.

The patients were asked to mark the positions at which a distortion wasobserved, by using a mouse connected to the Laptop computer as disclosedin detail hereinabove for the flash test. All the test data were storedin the laptop computer for further processing and analysis, as disclosedin detail for EXPERIMENT 1 hereinabove.

The results of EXPERIMENT 2 were then processed as follows. The computeranalyzed the position of the markings by the patient in response to thepresentation of test patterns having an AD, and classified the responsesas follows. Turning back to FIGS. 13 and 14, for horizontal testpatterns if the distance D6 (FIG. 13) is smaller than 2.83°, theposition of the marked point 750 is defined as being due to an AIOD.Similarly, for vertical test patterns, if the distance D7 (FIG. 14) issmaller than 2.83°, the position of the marked point 850 is defined asbeing due to an AIOD.

If, in response to the presentation of a test pattern including an AD,all the positions marked by the patient are defined to be due to an AIODusing the definition as disclosed hereinabove, the response isclassified as an A type response (indicating that all of the positionsmarked by the patient are considered to be due to an AIOD).

After determining the response type for all of the patient's responsesevoked by the presentation of test patterns including an AD, thecomputer further calculated the following parameters. For all of thetest patterns including an AD with the same height H, the computercomputed the value A_(H), wherein A_(H) is the percentage of responsesclassified as A type responses out of the total number of test patternspresented to the patient which contained an AD with a height H.

For example, if the patient was presented with twenty (20) test patternshaving an artificial distortion with a height of H=0.28° (represented asdegrees of the cone angle for a distance of 50 centimeters of the testedeye from the display on which the test patterns are presented), and five(5) responses out of all the patient's responses to the presentation ofthese twenty test patterns were classified as A type responses, thenA_(0.28)=25%.

After performing various different empirical calculations based on theanalysis of results of the patients tested in EXPERIMENT 2, thefollowing criterion was selected for determining if the patient belongsto the group having CNV, or belongs to the group having AMD with HRC,based on the results of the test patterns having ADs with a height of0.28° (it is noted that the data from the results of the test patternshaving ADs with heights of 0.19° and 0.22° was not used for establishingthe criterion below):

-   -   A patient belongs to the group with CNV if A_(0.28)<75%

If A_(0.28)≧75%, the patient belongs to the group having high riskcharacteristics AMD (AMD with HRC group).

When this patient classification criterion is applied to the testresults of all the patients tested in EXPERIMENT 2, the results were asindicated in TABLE 2 below. TABLE 2 Patients Patients ophtalmologicallyophtalmologically diagnosed as diagnosed as having having CNV AMD withHRC Total Patients for 18 6 24 which A_(0.28) < 75% Patients for 2 37 39which A_(0.28) ≧ 75% Total 20 43 63Calculated sensitivity 90%Calculated specificity 85%P < 0.001

It will be appreciated by those skilled in the art that the specificclassification criteria disclosed hereinabove for classifying patientsas belonging to specific different AMD disease progression groups, aregiven by way of example only and are not intended to limit the scope ofthe invention. Other different criteria may be empirically determinedand used by modifying or fine tuning the parameters of the test or theparameters of the test patterns used in the test. Systematically varyingone or more of the parameters of the test or of the test patterns usedtherein may be therefore used to fine tune or improve or optimize thetest to yield better or improved classification criteria. Suchsystematic variations are known to those skilled in the art, and aretherefore not described in detail hereinafter.

It is noted that while in the non limiting examples of the embodimentsof the competition method of the present invention which are describedin EXPERIMENT 1 and EXPERIMENT 2 disclosed hereinabove, the data usedfor distinguishing or classifying the tested individuals into differentgroups was taken from a group of test patterns having an AD of a certainselected height (the group of data obtained using test patterns with ADshaving a height H=0.19 in EXPERIMENT 1 and the group of data using testpatterns with ADs having a height H=0.28 in EXPERIMENT 2), this is notmandatory and other embodiments of the present invention may usedifferent or additional classification criteria based on processing ofthe results obtained from the presentation of test pattern groups havingdifferent artificial distortion heights.

For example, in accordance with other possible embodiments of theinvention it may be possible to use classification criteria which usedata from more than one group of test patterns having ADs of differentheights. For example, using the data obtained in EXPERIMENT 2, one mayuse a classification criterion that classifies a patient as having AMDwith HRC if A_(0.28)≧m and A_(0.22)≧n, and classifies the patient ashaving CNV if A_(0.28)<m and A_(0.22)<n, wherein m and n are percentagevalues which are empirically determined to give desired or acceptablelevels of specificity and sensitivity.

Moreover, other classification criteria may be used which may use thevalues of A_(H) computed from results of two or three groups of testpatterns presenting ADs with H=0.28, H=0.22 and H=0.19. For example, onemay used weighted results in the classification criterion.

An exemplary (non-limiting) form of such criteria using weighted resultsmay be, the patient may be classified as having AMD with HRC if:(αA _(0.28) +βA _(0.22) +γA _(0.19))≧q

-   -   and as having CNV if:        (αA _(0.28) +βA _(0.22) +γA _(0.19))<q    -   wherein α, β, and γ are empirically determined weighting        factors, and q is an empirically determined number.

The above criteria and other empirically determined criteria may be usedto implement the classification of the tested individuals into groupshaving different clinical stages of AMD (or other retinal or choroidalpathologies).

It will thus be appreciated that while the results of EXPERIMENT 1 andEXPERIMENT 2 demonstrate that it is possible to classify patients intogroups having different clinical stages of AMD by using the responses ofthe tested patients to the presentation of test patterns havingartificial distortions with a single AD height (for example, the testpatterns having H=0.19 of EXPERIMENT 1 or the test patterns havingH=0.28 of EXPERIMENT 2) it may also be possible to use within a singletest patterns having ADs with more than one height or amplitude and toprocess the patient responses data to classify the tested patients withproper modification of the classification criteria used.

It is noted that while the “competition” method of using differentgraded distortion magnitudes for assessing the severity, or themagnitude, or the dimensions of a retinal or choroidal lesion may bebased on the use of artificial distortions included in the segmentedtest patterns having different graded distortion heights as disclosedhereinabove, other types of graded artificial distortions having variousmagnitudes or amplitudes or size may also be used in the presentinvention.

Furthermore, while the competition tests disclosed hereinabove includedthe use of linear and distorted segmented test patterns, many othertypes of test patterns may also be used for implementing embodiments ofthe present invention, the test patterns may include but are not limitedto, non-segmented (continuous) lines like any of the types disclosedhereinabove with respect to the MCPT test, and may include but are notlimited to straight lines, curved lines, straight or curved lines havinga distorted portion or part, or the like. The parts of the test patternswhich are distorted may be curved like part of an elliptical curve, orparabolic curve, or an undulating curve, or any other suitable curveshape that may mimic the appearance of a distortion perceivable by apatient having a retinal lesion. Additionally, the distorted part of thetest pattern (irrespective whether the test pattern is segmented ornon-segmented) may be configured to have a linear shape, such as forexample, a triangular distortion shape, or the like. Moreover, thesegments (or alternatively the continuous part of the test pattern)comprising the distortion may be arranged as any desired type ofdistortion having any suitable shape.

In another example, in accordance with other embodiments of the presentinvention it may be possible to use artificial distortions with atriangular shape (not shown) having graded heights of the triangle-likedistortion, or curved artificial distortions in which the segments ofthe artificial distortion are arranged along non-linear curves otherthan an ellipse and having graded curve parameters. Such non-linearcurves may include but are not limited to parabolas, irregular curves,and curves having multiple extremum points.

Thus, the shapes, curvature, dimensions and magnitudes of the artificialdistortions disclosed hereinabove, illustrated in the drawing figuresand used in the experiments, are given by way of example only and arenot obligatory to practicing the invention. It is therefore noted thatmany other types of artificial distortions and test patterns havingother different parameters may also be used in practicing the inventionall of which are considered to be included within the scope of thepresent invention.

It is noted that while the distortion type used in EXPERIMENT 1 andEXPERIMENT 2 is symmetrical (with respect to the minor axis of the halfellipse curve 662 used for determining the position of the center points640C and 644C of the segments 640 and 644, respectively, illustrated inFIG. 12), the distorted part of the curve need not necessarily besymmetrical. Thus, the distortion types usable in different embodimentsof the present invention (irrespective of whether the test pattern issegmented or non-segmented) may be a symmetrical distortion or anon-symmetrical distortion.

For example, possible embodiments of the methods and test patterns ofthe invention it may include, inter alia, embodiments in which one ormore of the following test parameters may be varied: the number ofsegments in the test patterns, the segment size and/or shape (forexample, circular shapes may be used instead of square segments), thesegment shape, the distance between segments, the size and/or shapeand/or amplitude, and/or the longitudinal dimension of the artificialdistortion along the test pattern (the width of the distortion), and/orcurvature of the artificial distortion (including the curvature degreeand/or curvature direction of the artificial distortion), the colorand/or luminosity, of the test patterns and/or of the background onwhich the test patterns are displayed or presented to the patient, thesequence of presentation of the test patterns (including fixedsequences, random sequences, and pseudo-random sequences of test patternpresentations), the positioning of the AD within the test pattern, theAD magnitudes or amplitudes used in the test, the duration ofpresentation of the test pattern to the patient in the flash method, themethod of position marking used by the patient for reporting theposition of the observed distortions, the number, type, and sequence ofthe test patterns included in a test, or the like.

It will be appreciated by those skilled in the art that if one or moreof the parameters of the test patterns or of the artificial distortionsused are modified, the methods and criteria used for processing the dataand for analyzing the results may have to be adapted to the changesmade.

For example, in accordance with one possible embodiment of the presentinvention, the artificial distortions used may be graded according totheir width or longitudinal dimension along the test pattern. Returningbriefly to FIGS. 12-14, the artificial distortions may also graded bygraded changing of the longitudinal dimension of the artificialdistortion along the test pattern. For example, the distance MA (FIG.12) may be varied in a graded manner in different ADs instead of thedistance H (FIG. 12). In such a case it may be necessary to adapt thedistance from the center of the AD which is used as a criterion todecide if a position marked by the tested individual is assumed to bedue to the artificial distortion (or defined as an AIOD as disclosed indetail hereinabove).

For example, in accordance with one possible embodiment of theinvention, one may use three different ADs in a test. All the ADs usedhave the same distance H (such as, but not limited to, 0.22°), but eachAD may have one of three possible values of the distance MA, such as,but not limited to, 1.92°, 2.62°, and 3.32°. This may be achieved, forexample, by displacing three, five, and seven segments of the testpattern 630, respectively, vertically above the line 660 of FIG. 12,using a suitable half ellipse curve, or by suitably increasing thedistance D4 between the segments 638, 640, 642, 644, and 646 withoutchanging the distance between each of the segments 640 642 and 644 andthe straight line 660, or by any suitable combination of the aboveexemplary methods, or by any other method for increasing the width orlongitudinal dimension (on the axis labeled X of FIG. 12) of the ADalong the test pattern 630.

In such a case, it may be desired to modify the criterion of distance ofthe marked position from the center point of the AD for each of thethree different graded forms of the AD. For Example, the criteriondistance for ADs having MA=1.92° may be 2.83° as disclosed above, whilethe criterion distance used for ADs having MA=2.62°, and MA=3.32° may be3.53°, and 4.23°, respectively (all cone angles assuming a distance ofapproximately 50 centimeters from the tested eye and the screen 112).

Similarly, if any other parameters of the test patterns are changed, orthe type and/or density of the grid which they may form on the retina ifthey were all simultaneously projected thereon are changed, it may ormay not be necessary to suitably change or adapt the processing of thedata, such as, but not limited to, the proximity criteria used forprocessing the responses to pairs of test patterns projected, or thelike.

Furthermore, it will be appreciated by those skilled in the art thatwhile the shape and dimensions of the ADs used in the experiments may becomputed or determined using mathematical methods for constructing thetest patterns including ADs (such as in the exemplary embodiment forcomputing of the position of the center points of the segments 640 642and 644 of FIG. 12 using a half ellipse curve computation), it may alsobe possible to use test patterns having ADs which are empirically foundto give a satisfactory sensitivity and selectivity in classificationstudies similar but not identical to the studies disclosed in EXPERIMENT1 and EXPERIMENT 2 above.

In such studies one may possibly test many different types ofarbitrarily or non-computationally created artificial distortions inorder to empirically define a set of ADs which yields satisfactoryclassifications of AMD stages. Such artificial distortions may beconstructed to differ one from the others in shape or dimensions orcolor or any other single or multiple characteristics of the ADs.

For example, if one uses within the same test an ellipsoidaly shaped AD,a triangularly shaped AD and a rectangularly shaped AD, and it is foundthat each of these ADs has a different efficacy as a competing stimulus,such AD combinations may also be practically used in the classificationtests of the present invention.

It is noted that it may also be possible to use in the tests of thepresent invention ADs in which the AD may include arbitrarily selectedchanges in any visually perceivable characteristic(s) of the testpattern or of parts thereof. Such changes may be in the color orbrightness or blurriness or in any other suitable perceivablecharacteristic of the test pattern or part thereof, as long as the usedsets of AD have been empirically tested and proven to give satisfactoryperformance is clinical tests in humans with eye disease.

Moreover, while the precise mechanism underlying the competitionphenomenon disclosed herein is not known, it may be possible that whenthe patient is simultaneously presented with multiple stimuli, there isa “competition for attention”. It may therefore be possible that when apatient is simultaneously exposed to multiple sensory stimuli there is acertain probability that the more prominent or noticeable or largerstimulus will be preferentially noticed (and therefore preferentiallyreported by the patient.

When the two stimuli are of the same sensory modality, such as forexample in the cases in which a test pattern including an AD isprojected on a retinal position having a retinal lesion, the perceiveddistortion which is of a larger magnitude or which is more noticeable orperceived as larger or more prominent may be statisticallypreferentially perceived by the patient (and therefore may bestatistically preferentially reported by the patient).

It may therefore be possible, in accordance with additional embodimentsof the present invention to use in the “competition method” otherdifferent types of sensory stimuli for competing with the PROD,including but not limited to, visual stimuli, auditory stimuli,somatosensory stimuli (including but not limited to various temperaturestimuli, touch stimuli, pressure stimuli, itch stimuli, or the like),kinesthetic stimuli such as moving various different limbs or digits orother organs, various different pain stimuli, or any other suitablesensory stimuli having various different modality.

Such sensory stimuli of various differing sensory modalities aregenerally referred to as competing stimulus (CS) hereinafter. In thepresent application, the definition of a competing stimulus is anysensory stimulus which may be delivered or applied or presented to atested patient and which may affect the probability that the patientwill report a PROD when a test pattern is presented to the patient at alocation such that the image of the test pattern is projected on alesioned retinal or choroidal region.

The different sensory stimuli may be administered or applied orpresented to the patient before and/or simultaneously with thepresentation of the visual test patterns disclosed hereinabove in detailor with the presentation of other suitable different visual testpatterns. These different sensory stimuli may possibly function as“distracting stimuli” or as “competing stimuli” that compete forpatient's attention for obtaining results which are similar (though notnecessarily identical) to the results of the competition experimentsusing visual AD's as disclosed hereinabove.

Additionally, one or more of the parameters of these additional sensorystimuli may be varied systematically or graded in differentpresentations of the stimuli. By varying one or more of the parametersof the additional sensory stimuli presented with or before or after theprimary visual test patterns (such as, but not limited to the linearsegmented test pattern 322 of FIG. 3, or the test patterns 382 of FIG.5B disclosed hereinabove), and by recording and analyzing the patient'sresponses, it may be possible to empirically establish classificationcriteria for diagnosing a patient as belonging to a group with a definedstage of the disease. For example, using such criteria it may bepossible to distinguish between different clinically distinguishablestages of AMD (such as but not limited to the different AMD stagesdisclosed hereinabove in EXPERIMENT 1 and EXPERIMENT 2).

It will be appreciated by those skilled in the art that such criteriamay be different than the empirical criteria disclosed hereinabove forthe use of artificially distorted test patterns disclosed for EXPERIMENT1 and EXPERIMENT 2 hereinabove.

Thus, in accordance with one exemplary embodiment of the invention, thedistracting stimulus may be an auditory stimulus. For example, thepatient may perform a modified version of an MCPT test in which anauditory stimulus may be delivered to the patient before, during, orafter the presentation of a visual test pattern. The auditory stimulusmay be delivered to the patient by using earphones (not shown) orsuitable speakers, or the like. The auditory stimulus may be in the formof a click, or a beep, or a pure sine wave having a finite duration, ora telephone-like ringing, or any other suitable type of auditorystimulus known in the art. The auditory signal may be delivered to thepatient before, during, or after the presentation of a test pattern (thetest pattern may or may not include an AD) to a tested eye of thepatient. If the test pattern is presented at a location such that thepatient may perceive a PROD, the delivery of the auditory stimulus maydistract the patients attention. By repeating the presentation of thetest pattern together with the auditory stimulus, varying (grading) oneor more of the parameters of the auditory stimulus delivered, andrecording the patient's responses to the presentation of the teststimuli it may be possible to analyze the competition of the auditorystimulus with the PROD and to empirically determine classificationcriteria for various AMD stages, or for other stages of other differentretinal pathologies or diseases.

The parameters of the auditory stimulus that may be varied (graded) indifferent presentations of test patterns may be but is not limited toone or more of the amplitude, duration, frequency (or frequency rangeand content for stimuli including a range of frequencies), or waveformof the auditory stimulus. Additionally, it may be possible to use agroup of different auditory stimuli which are empirically selected onthe basis of having different psychophysical efficacy as distracting orcompeting stimuli.

Experiment 3

This experiment was performed to test different types of auditorystimuli for their efficacy as competing stimulus (CS), in accordancewith yet another embodiment of the present invention. The study includedthree tested individuals having normal retinas (as ascertained by fullophtalmological examination as disclosed hereinabove). Each one of thetested individuals was subjected to five different tests (designated astests 1-5). Each of the tests 1-5 included presenting a total of thirtyeight (38) test patterns to the tested individual using the flash methodas disclosed in detail hereinabove. The test patterns were segmentedstraight lines as disclosed in detail hereinabove for EXPERIMENT 2. Ofthe thirty eight test patterns presented in each test, nineteen testpatterns were vertical and the other nineteen test patterns werehorizontal. Each of the 38 test patterns included an AD having a heightof 0.12°, as disclosed hereinabove. The position of the AD within thetest pattern was randomized using an LUT as disclosed hereinabove.

Reference is now made to FIG. 15 which is a schematic diagramillustrating a system useful for carrying out an eye test to detect andor assess an eye disease using auditory competing stimuli in accordancewith another embodiment of the present invention. The system 305 issimilar to the system 105 disclosed hereinabove, except that the screen212 of the display device 115 was a touch sensitive screen, and thetested subject 100 marked the positions of the ADs or other perceiveddifferences on the screen 212 using his finger instead of using themouse 125, and that the system 305 also included a stereophonicheadphones set 211.

For the duration of the tests, the tested subject 100 was wearing theheadphones set 211. In all the tests performed in EXPERIMENT 3 andEXPERIMENT 4, the headphones set 211 were model MDR-305 stereophonicheadphones, commercially available from Sony Corp., Japan.

It is, however noted, that any other suitable sound source may be usedfor performing the method of the present invention, including but notlimited to monoaural sound sources, single earphones worn by the testedindividual, various types of loudspeakers such as one or moreloudspeakers which are built into or form part of the computer system105 or 305, one or more loudspeakers positioned in the room in which theindividual 100 is being tested, or any other single or multiple soundsources known in the art.

The headphones set 211 were suitably connected to the line output of thesound card (not shown) installed in the computer 110. The computer 110in this study was a Dell Latitude Laptop computer, model C600commercially available from Dell Computer Corporation U.S.A, and theoperating system was the Microsoft Windows 2000 Professional (Version5.0.2195 Service Pack 1, Built 2195) commercially from MicrosftCorporation, U.S.A. During all tests the distance between the screen 212and the tested eye was approximately 50 centimeters.

The sound card used for the production of the CS was the onboard soundcard hardware provided with the Dell Latitude C600 laptop computer (ESSMaestro PCI audio, from Engineering Software Services companies Fl,U.S.A). All Sound measurements were performed using the “Environmentalnoise measurement system” software (version 3.1.1.2) commerciallyavailable from Yoshimasa Electronic Inc., Japan, using the soundpressure level (SPL) measurement mode.

For measuring the sound pressure levels, a model MIC111 Maxxtroomni-directional microphone was used (commercially available fromGembird Electronics Ltd., Hong Kong). The microphone had a frequencyresponse of 15 Hz-13 KHz, an impedance of >2,200 Ohms, and a sensitivityof 58 dB±2 dB. The microphone was connected to the line-in audio inputjack of the laptop computer and the microphone was placed between thetwo earphones at a distance of approximately 3 millimeters from eachearphone.

In two of the tests conducted (TEST 1 and TEST 3) no sound was usedduring the test. These tests served as control tests.

In TEST 2, TEST 4 and TEST 5, sound was used as a competing stimulus(CS). The test pattern presentation duration was 160 milliseconds asdisclosed hereinabove. The duration of the sound used as the auditory CSwas 900 milliseconds. The auditory CS started at the time ofpresentation of the test pattern and ended 740 milliseconds after theend of the presentation of the test pattern on the screen 212.

Three different auditory CS types were used. In TEST 2 the auditory CSwas a sound having an increasing pitch (defined as sound type 1). Soundtype 1 was obtained by playing through the headphones set 211 the soundfile “SOUND20.WAV” taken from the Windows XP® sound library. The filewas played as the auditory CS through the headphones set 211 at a soundpressure level of 40 dB.

In TEST 4 the auditory CS was a synthesized telephone ring-like sound(defined as sound type 2) Sound type 2 was obtained by playing throughthe headphones set 211 the sound file “RINGIN.WAV” taken from theWindows XP® sound library. The intensity of the auditory CS was 40 dB.

In TEST 5 the auditory CS was a synthesized sound of electronic drumswhich was panned as if moving from the right side to the left side inspace, by changing the sound intensity in the left and right earphonesof the headphones set 211 (defined as sound type 3). Sound type 3 wasobtained by playing through the headphones set 211 the sound file“TestSnd.wav” taken from the Windows XP® sound library. The soundpressure level of the auditory CS was 40 dB.

In all tests the subject 100 was requested to mark all the perceiveddistortions in all the test patterns as disclosed in detail hereinabove.The tested subject marked the perceived distortions by touching thetouch sensitive screen 212 with his finger at the position at which adistortion or a difference or deviation from a reference segmentedstraight line was perceived.

The following parameters were recorded for analysis. A response in whichthe presented AD was detected and correctly marked (according to thecriteria as disclosed hereinabove for EXPERIMENTS 1 and 2) is recordedas “FOUND”.

A response in which the presented AD was not detected by the testedsubject 100 (according to the criteria as disclosed hereinabove forEXPERIMENTS 1 and 2) is recorded as “NOT FOUND”.

A response in which the position marked by the tested subject 100 wasfar from the location of the center of the AD (the criterion used herewas when the position marked was at a cone angle of more than 2 degreesfrom the center of the AD) is referred to as “REAL”, indicating that thetested subject did observe a distortion or difference which is assumednot to be due to the presence of the AD presented in the test pattern.

In analyzing the results, a “competition index” C_(I) was defined asfollows,C _(I) =F/(NF+R)

-   -   Wherein,    -   C_(I) is the competition index for sound type I (for example, C₁        is the competition index for sound type 1, C₂ is the competition        index for sound type 2, etc.),    -   F represents the number of test pattern presentations in the        test for which a “FOUND” response was recorded,    -   NF represents the number of test pattern presentations in the        test for which a “NOT FOUND” response was recorded, and    -   R represents the number of test pattern presentations in the        test for which at least one “REAL” response was recorded.

Higher values of C_(I) indicate a higher percentage of correctidentifications of the artificial distortions, while lower values ofC_(I) indicate a lower percentage of correct identifications of theartificial distortions.

The raw data of all test results in EXPERIMENT 3 is shown in TABLE 4below.

In TABLE 4, the first column lists the tested subject number (testsubjects 1, 2, and 3). The second column indicates the test number. Forthe column group labeled “Found”, the sub-column labeled H representsthe number of horizontal test patterns for which a “Found” result wasrecorded in the test indicated in the appropriate row, the sub-columnlabeled V represents the number of vertical test patterns for which a“Found” result was recorded in the test indicated in the appropriaterow, and the sub-column labeled T represents the total number of testpatterns (horizontal and vertical) for which a “Found” result wasrecorded in the test indicated in the appropriate row.

Similarly, for the columns group labeled “Not Found”, the sub-columnlabeled H represents the number of horizontal test patterns for which a“Not Found” result was recorded in the test indicated in the appropriaterow, the sub-column labeled V represents the number of vertical testpatterns for which a “Not Found” result was recorded in the testindicated in the appropriate row, and the sub-column labeled Trepresents the total number of test patterns (horizontal and vertical)for which a “Not Found” result was recorded in the test indicated in theappropriate row, and for the columns group labeled “Real”, thesub-column labeled H represents the number of horizontal test patternsfor which a “Real” result was recorded in the test indicated in theappropriate row, the sub-column labeled V represents the number ofvertical test patterns for which a “Real” result was recorded in thetest indicated in the appropriate row, and the sub-column label Trepresents the total number of test patterns (horizontal and vertical)for which a “Real” result was recorded in the test indicated in theappropriate row. TABLE 4 Tested Subject and Test “Found” “Not Found”“Real” R + F/ Number H V T H V T H V T NF (NF + R) 1. test 1 19 12 31 03 3 0 4 4 7 4.43 test 2 14 14 28 1 1 2 4 4 8 7 4.00 test 3 17 14 31 0 00 2 5 7 10 3.10 test 4 14 14 28 0 0 0 5 5 10 10 2.80 test 5 17 14 31 1 12 1 4 5 7 4.43 2. test 1 15 14 29 1 5 6 3 0 3 9 3.22 test 2 16 9 25 3 1013 0 0 0 13 1.92 test 3 14 16 30 1 1 2 4 2 6 8 3.75 test 4 10 10 20 5 712 4 2 6 18 1.11 test 5 2 8 10 13 10 23 4 1 5 28 0.36 3. test 1 12 15 274 1 5 3 3 6 11 2.45 test 2 10 8 18 7 5 12 3 5 8 20 0.90 test 3 14 13 275 3 8 0 3 3 11 2.45 test 4 14 10 24 5 6 11 0 3 3 14 1.71 test 5 12 14 266 3 9 1 2 3 12 2.17

The columns labeled R+NF and F/(NF+R) show the values of theseexpressions (calculated as disclosed in detail hereinabove) for the testindicated in the appropriate row.

Summary of the Results of Experiment 3

The raw results shown in TABLE 4 above were further pooled and averagedas shown below.

1. The value of the pooled competition index for all the tests with noauditory competing stimulus was calculated as follows, the results fromTEST 1 and TEST 3 (the tests with no auditory competing stimuli) of allthree test subjects (tested subjects 1, 2, and 3), and the computedQ_(I) values for all six tests were averaged. The resulting mean was3.23±0.77 (Mean±S.D.; n=6 tests).

2. The value of the pooled competition index for all the tests in whichauditory competing stimuli was presented was calculated as follows: Theresults from TEST 2, TEST 4 and TEST 5 (the tests with auditorycompeting stimuli) of all three test subjects (tested subjects 1, 2, and3), and the Q_(I) values for all nine tests were averaged. The resultingmean was 2.16±1.38 (Mean±S.D.; n=9 tests).

The results for each one of the tests (TEST 1-TEST 5) were also averagedby averaging the competition index calculated for all three testedsubject as follows:

3. The value of the calculated competition indexes for TEST 1 (noauditory competing stimulus) was averaged for all three tested subjects(tested subjects 1, 2, and 3). The computed Q₁ values for the tests wereaveraged. The resulting mean was 3.37±0.77 (Mean±S.D.; n=3 tests).

4. The value of the pooled competition index for all the tests in whichthe presented auditory competing stimuli number was Sound type 1 wascalculated as follows: The results from TEST 2 (the test in which theauditory competing stimulus was sound type 1) for all three testsubjects (tested subjects 1-3) were averaged, and the mean Q_(I) valuefor TEST 2 in all three subjects was 2.27±1.1 (Mean±S.D.; n=3 tests).

5. The value of the calculated competition indexes for TEST 3 (noauditory competing stimulus) was averaged for all three tested subjects(tested subjects 1, 2, and 3). The computed Q_(I) values for the testswere averaged. The resulting mean was 3.10±0.67 (Mean±S.D.; n=3 tests).

6. The value of the pooled competition index for all the tests in whichthe presented auditory competing stimuli number was Sound type 2 wascalculated as follows: The results from TEST 4 (the test in which theauditory competing stimulus was sound type 2) of all three test subjects(tested subjects 1-3), and the Q_(I) values for all three tests wereaveraged. The resulting mean was 1.88±0.86 (Mean±S.D.; n=3 tests).

7. The value of the pooled competition index for all the tests in whichthe presented auditory competing stimuli number was Sound type 3 wascalculated as follows: The results from TEST 5 (the test in which theauditory competing stimulus was sound type 3) of all three test subjects(tested subjects 1-3), and the Q_(I) values for all three tests wereaveraged. The resulting mean was 2.32±2.04 (Mean±S.D.; n=3 tests).

To summarize, the results of EXPERIMENT 3 demonstrate that auditorystimuli of different types may reduce the ability of the testedindividual to perceive and/or report an artificial distortion in avisually presented test pattern. The mean competition index for alltests without an auditory competing stimulus (no sound), is 3.23±0.77(Mean±S.D.; n=6 tests) as compared to a lower value of 2.16±1.38(Mean±S.D.; n=9 tests) in the tests in which a competing auditorystimulus was presented to the tested subject. It may also be seen fromthe above presented results that different types of auditory stimulihaving different characteristics may have different efficacy incompeting against the presented visual stimuli (the AD). For example,from the three different types of auditory stimulus, sound type 2 wasthe most efficient in competing with sound types 1 and 3 have lowerefficacy than sound type 2. This was consistent for all three testedsubjects.

While the physiological or psychophysical basis for this phenomenon isnot presently clearly understood, it may be possible that the differenttypes of sound have different efficacy as distracting stimuli indistracting the attention of the tested subject from the visual stimulipresented in the test. It may therefore be concluded that sounds havingvarious different characteristics may be used for assessing orquantifying the severity of retinal or choroidal lesions orabnormalities.

Experiment 4

This experiment was performed to test the ability of a specific form ofauditory competing stimulus presented at different sound intensities tocompete in a graded manner with visual stimuli for patient attention intests requiring the reporting of artificially introduced distortions invisual test patterns.

The same three individuals from EXPERIMENT 3 were tested. The tests inexperiment 4 were performed as described in detail for EXPERIMENT 3hereinabove. Each of the three tested individuals having normal retinaswere given three consecutive tests (TEST 6, TEST 7 and TEST 8). Eachtest included 38 test patterns (19 vertical and 19 horizontal) performedas disclosed for TEST 4 of EXPERIMENT 3, except that the sound pressurelevels used were different than the sound intensity used in TEST 4. Theauditory CS was Sound type 2, obtained by playing through the headphonesset 211 the sound file “RINGIN.WAV” taken from the Windows XP® soundlibrary.

In all the tests included in EXPERIMENT 4 (tests 6, 7 and 8), theduration and the timing of the auditory CS was as disclosed in detailfor TEST 4 of EXPERIMENT 3.

In TEST 6 the sound pressure level of the CS was 35 dB, in TEST 7 thesound pressure level of the CS was 45 dB, and in TEST 8 the soundpressure level of the CS was 50 dB.

The raw test results for EXPERIMENT 4 are given in TABLE 5 below, (thecolumn arrangement and abbreviations in TABLE 5 are as described forTABLE 4).

The competition index Q_(I) was calculated for all tests (as given inthe rightmost column of TABLE 5). For each test the computed Q_(I)values from all three tested individuals were averaged and the resultsare summarized in TABLE 6 below. TABLE 5 Tested Subject and Test “Found”“Not Found” “Real” R + F/ Number H V T H V T H V T NF (NF + R) 1. test 617 13 30 0 4 4 2 2 4 8 3.75 test 7 16 13 29 3 5 8 0 1 1 9 3.22 test 8 1410 24 4 9 13 1 0 1 14 1.71 2. test 6 15 8 23 3 5 8 1 6 7 15 1.53 test 710 9 19 7 9 16 2 1 3 19 1.00 test 8 8 10 18 10 8 18 1 1 2 20 0.90 3.test 6 16 15 31 2 2 4 1 2 3 7 4.43 test 7 13 8 21 4 7 11 2 4 6 17 1.24test 8 11 10 21 6 8 14 2 1 3 17 1.24

TABLE 6 Sound Pressure averaged Q₁ value TEST level for all testedsubjects NUMBER of Auditory CS Mean ± S.D. (n = 3) TEST 6 35 dB 3.24 ±1.514 TEST 7 45 dB 1.82 ± 1.221 TEST 8 50 dB 1.28 ± 0.409

The results of EXPERIMENT 4 indicate that when a given sound type(specifically, sound type 2) is presented to the tested individuals atdifferent sound pressure levels during the visual testing as describedhereinabove, the computed competition index is a function of the soundpressure level of the auditory competing stimulus. As is shown in TABLE5 and TABLE 6 above, there is a direct correlation between soundpressure level and the ability of the tested individual(s) to correctlyreport the positions of the AD in the test patterns (in accordance withthe specific criteria used in the tests). Thus, while the physiologicalor psychophysical basis for this phenomenon are not presently clearlyunderstood, it may be possible that the different intensities of soundhave different efficacy as distracting stimuli in distracting theattention of the tested subject from the visual stimuli presented in thetest. It may therefore be concluded that sounds having graded intensityvalues may be used for assessing or quantifying the severity of retinalor choroidal lesions or abnormalities.

Reference is now made to FIG. 16 which is a schematic block diagramillustrating a system for applying visual tests and competing sensorystimuli to a test subject, in accordance with an embodiment of thepresent invention.

The system 650 may include a visual test-pattern presenting unit 660 forpresenting test patterns to a test subject (not shown), and a competingsensory stimuli generating unit 662 for presenting the tested subjectcompeting sensory stimuli. The visual test-pattern presenting unit 660and the competing sensory stimulus generating unit 662 may be suitablyoperatively coupled to a controller/processor unit 664. Thecontroller/processor unit 664 may control and coordinate the presentingof visual and competing sensory stimuli to the test subject by thevisual test-pattern presenting unit 660 and the competing sensorystimuli generating unit 662, respectively.

The system 650 may further include one or more user input device(s) 666,one or more output device(s) 668 and a storage unit 670 for storingdata. The user input device(s) 666, the output device(s) 668, and thestorage unit 670 may be suitably connected to the controller/processorunit 664.

The visual test-pattern presenting unit 660 may be any type of unit ordevice suitable for presenting visual test patterns to a test subject asdisclosed hereinabove and as known in the art. For example, the visualtest-pattern presenting unit 660 may be a computer with a coupleddisplay device, such as a computer, or a desktop computer or a laptopcomputer or a workstation or any other device known in the art that iscapable of controllably presenting test patterns to a test subject. Forexample, the visual test-pattern presenting unit 660 may be any of thesystems 105 of FIG. 1 or the system 600 of FIG. 10, or any other type ofdisplay or screen based device known in the art, or any other type ofdevice capable of scanning a beam of light into an eye, including, butnot limited to, SLO devices and head up display (HUD) devices known inthe art.

If the visual test-pattern presenting unit 660 includes a surface or ascreen capable of displaying images of the test patterns (and fixationtarget, if required), the display may be any type of suitable displayknown in the art, including but not limited to a cathode ray tube (CRT)type display device, a liquid crystal display (LCD), a light emittingdiode (LED) or organic light emitting diode (OLED) based display device,a plasma display device, a mechanical or micro-electromechanical (MEMS)based display device, or the like. Generally, any suitable device thatmay be adapted for displaying or projecting images on a surface ordirectly projecting images into an eye, or of controllably scanning abeam of light into an eye is considered to be within the scope of thepresent invention.

Generally, the competing sensory stimulus generating unit 662 may be anytype of device or system or unit which is capable of delivering sensorystimuli to the individual which is being tested using the system 650.

For example, in accordance with one possible embodiment of theinvention, the competing sensory stimulus generating unit 662 may be asystem or device for delivering auditory stimuli (sound stimuli) to thetested individual, such as but not limited to a sound source suitablycoupled to controller/processor unit 664. In the exemplary embodimentdisclosed in detail hereinabove and illustrated in FIG. 15, thecompeting sensory stimulus generating unit 662 may include a computeradd-on sound card (not shown in FIG. 15) installed in the computer 110and coupled to the pair of headphones 211. It will be appreciated bythose skilled in the art, that many other types of sound sources may beused as is disclosed in detail hereinabove or as is known in the art.Thus, any suitable type of sound source which may be used to generatesound stimuli in a controlled manner may be used in the presentinvention.

In accordance with other possible embodiments of the present invention,the competing sensory stimulus generating unit 662 may be any suitabledevice for delivering tactile sensory stimuli, or any suitable devicefor delivering other types of somatosensory stimuli capable of competingwith the visual stimuli delivered by the system 650 to the testedindividual, such as, but not limited to, nociceptive stimuli, tactilestimuli, thermal stimuli (temperature change related stimuli), pressurestimuli, mechanical stimuli delivered to the tested individual (such as,but not limited to, mechanically delivered vibrations applied to theskin of the tested individual), or any other suitable stimuli havingother suitable sensory modalities.

For example, in accordance with one possible embodiment of theinvention, the competing sensory stimulus generating unit 662 mayinclude an electrically powered vibrator (not shown) or probe which ismechanically coupled or attached or put in contact with the skin of thetested individual and which is suitably connected to thecontroller/processor unit 664. For example, the vibrator may be a smallflat piezoelectric transducer which put in contact with the skin of thetested individual is attached to the skin (of the finger, or the hand,or any other suitable body part of the tested individual) using a bandor strap of flexible material (not shown). In operation, vibrationshaving different vibration amplitudes or frequencies may be delivered tothe skin of the tested individual before, during or after thepresentation of the test patterns as disclosed hereinabove. Many othertypes of vibrating devices or probes or other graded mechanical stimulusdelivering devices may also be adapted for used with the presentinvention, as is well known in the art.

In accordance with another possible embodiment of the invention, thecompeting sensory stimulus generating unit 662 may be an electricallyoperated heating element, or Peltier device, (not shown in detail) whichmay thermally coupled to the skin and which may be used to controllablydeliver heat or cold stimuli to the skin of the tested individualbefore, during or after the presentation of the test patterns asdisclosed hereinabove. Additionally, a suitable laser device may be usedto deliver heating pulses having different graded parameters to an areaof the skin of the tested individual which may be used as thermalcompeting stimuli.

In accordance with another possible embodiment of the invention, thecompeting sensory stimulus generating unit 662 may be an electricallyoperated heating element, or Peltier device (not shown in detail) whichmay thermally coupled to the skin and which may be used to controllablydeliver thermal (heat or coldness) stimuli to the skin of the testedindividual before, during or after the presentation of the test patternsas disclosed hereinabove.

It is noted that the methods and devices for delivering various gradedor non-graded) sensory stimuli to a patient or test subject are wellknown in the art, are not the subject matter of the present invention,and are therefore not disclosed in detail hereinafter. Generally, thecompeting stimuli (CS) of the method and systems of the presentinvention may be delivered to the test subject using any suitable deviceknown in the art for controllably delivering such sensory stimulation toa tested individual.

The user input device(s) 666 may be one or more user interface deviceswhich may be used by the tested individual to provide input to or tointeract with the system 650 during the performing of tests. The inputdevice(s) 666 may include but are not limited to, a computer pointingdevice, a mouse, a keypad, a keyboard, a touch sensitive screen (usablein conjunction with a suitable stylus or with a finger, or the like), atouch sensitive pad, other types of touch sensitive devices, a lightpen, a stylus, a joystick, and any suitable combination of the abovelisted input devices, or any other suitable type of input device knownin the art.

The output device(s) 668 may include but are not limited to a displaydevice for providing instructions or images, or test patterns to thetested individual, a printer for providing hardcopy of the test resultsor of test schedules or of patient demographic or other data (including,but not limited to, raw test results, and/or processed test results, andor diagnostic information, in graphic form or alphanumeric form or anyother symbolic form).

The storage unit(s) 670 of the system 650 may be any suitable type ofstorage known in the art and usable for storing data and/or programs foroperating the system 650 or the controller/processor unit 664, and orraw or processed test results and the like. For example, the storageunit(s) 670, may include one or more solid state memory devices such as,but not limited to, RAM, DRAM, SDRAM ROM, RDRAM, FLASH, and compactFLASH memory devices, or combinations thereof. The storage unit(s) 670may also include other types of storage devices having fixed orremovable storage media, such as, but not limited to, magnetic drives,optical drives, magnet-optical drives, solid state drives having fixedor removable solid state media, holographic drives or storage devices,or the like.

It is noted that while the system 650 is shown is a specificconfiguration illustrated in FIG. 16, many other configurations thereofmay be implemented. For example, while the controller/processor unit 664of FIG. 16 is illustrated as a separate unit, the controller/processorunit 664 may be included as part of the visual test-pattern presentingunit 660 or of the visual test-pattern presenting unit 660. In otherembodiments of the system 650, the visual test-pattern presenting unit660 and/or the visual test-pattern presenting unit 660 may includeadditional controllers and/or processors (not shown in detail in FIG.16). Furthermore, the system 650 may be (optionally) suitably connectedvia one or more communication line(s) 672 to other computers (not shown)or to a computer network such any of the networks disclosed hereinabove(including but not limited to, a LAN, a PAN, a WAN, a VPN or the like).

Thus, while in accordance with one embodiment of the present invention,the system 650 or the other systems disclosed in the application, may bea standalone system, such as a system which may be used in the office ofan eye physician or in a clinic of an ophtalmologist or other eyespecialist, for testing individuals, for patient screening, or for otherdiagnostic or treatment follow-up purposes, or for any other suitable.In this embodiment the testing and processing of the data, and thereporting of the test results may all be performed by the system.

In accordance with other embodiments of the invention, the systems 650,or 105 may be a simple and relatively inexpensive system for home use bythe patient. In such embodiments it may be possible to process the databy the system and produce an output for the patient as disclosed indetail hereinabove, or it may be possible to send the processed testresults or the raw data itself using any the network types disclosedhereinabove. The analyzed test results or the raw data (or both) may becommunicated to a supervising physician's office or clinic or to acentral data bank in a hospital or in an or to any other suitable healthservice provider, or the like.

Additional Possible Types of Competing Stimuli

An additional type of usable competing stimulus is a visual stimulus. Inaccordance with another embodiment of the invention, a visual testpattern is presented to the patient (such as but not limited to thesegmented test patterns disclosed in EXPERIMENT 1 and EXPERIMENT 2 usingthe flash method of presenting the test pattern, as disclosed in detailhereinabove) and another visual stimulus is displayed on the samedisplay device at a different location than the location of the testpattern. For example, the additional (distracting or competing) visualstimulus may be a visual pattern such as but not limited to a knownsymbol or character or the like such as for example, the letter C, orthe number 5, or a graphic symbol (such as, for example, the symbol

), or any other suitable visual pattern or alphanumeric symbol orcharacter or graphic sign, or the like. This additional visual stimulusis referred to as a “distracting visual stimulus” (DVS) hereinafter.

In accordance with another embodiment of the present invention, the DVSmay be superimposed on part of the test pattern or may be separatelypresented on the display device. The DVS may or may not be presentedsynchronously with the test pattern. For example, if the test pattern ispresented using the above described flash method, the DVS may be flashedtogether with the test pattern for the entire duration of thepresentation of the test pattern, or may be presented before, and/orduring, and/or after the presentation of the test pattern. Thus, theduration of the presentation of the DVS may be equal to, or smallerthan, or larger than the duration of the presented test pattern.

In accordance with another embodiment of the present invention, the timeperiod of the presentation of the test pattern may fully or partiallyoverlap the time period of the duration of the DVS. The time period ofthe presentation of the DVS may, however, not overlap the duration ofpresentation of the test pattern, but may precede the time ofpresentation of the test pattern and may terminate before orsimultaneously with the beginning of the presentation of the testpattern.

In accordance with another embodiment of the present invention, the DVSmay also be any other type of visual pattern such as a picture ordigital photograph or digital representation, or image of a human face,or any other suitable object. The distracting capability of the DVS maybe related to the type or nature of the object presented in the DVS.

In accordance with another embodiment of the present invention, the DVSmay be a part of the test pattern. For example, if the test pattern is asegmented test pattern (such as but not limited to the test pattern 382of FIG. 5B), the DVS may include one or more of the segments of thesegmented test pattern 382.

In a non-limiting example, the DVS may be one or more segments of thetest pattern 382 which may be colored yellow, while all the rest of thesegments of the test pattern 630 may be colored white (all the segmentsof the test pattern 682 may be presented on a black background). Thus,the different color of the segments which are included in the DVS maydistract the attention of the patient or compete for attention with aPROD which may be observed by the patient when the test pattern 382 ispresented at a location on the screen 112 such that at least part of thetest pattern is projected on a retinal lesion. Similar to the results ofthe competition of the ADs introduced into the test pattern inEXPERIMENT 1 and EXPERIMENT 2, the presentation of this type of DVS(comprising yellow colored segments) may decrease the probability thatthe patient will report the PROD.

It is noted that while the exemplary embodiment disclosed hereinaboveuses segmented lines, the use of different colored DVS may also beapplied to any other type of usable test pattern, such as but notlimited to continuous lines (including straight or curved lines), or anyother suitable type of test pattern. For example, if the test pattern isa straight continuous line, the DVS may be a differently colored portionof the straight line.

In accordance with another embodiment of the present invention, the partof the test pattern the DVS may only partially overlap the test pattern.For example, if the test pattern used is similar to the test pattern 382of FIG. 5B, the DVS may be a short segmented line (not shown) which isgenerally orthogonal to the test pattern 382 and has six yellowsegments. One segment of the DVS may overlap one segment of the testpattern 382 such that the segment which is common to the DVS and thetest pattern is yellow.

It is noted that the color yellow is arbitrarily chosen as anon-limiting example and that any other suitable color may be used inother embodiment of the invention.

Reference is now made to FIGS. 17A-17K which are schematic diagramsillustrating exemplary forms of various different test patterns andcompeting visual stimuli which may be used in accordance with someembodiments of the present invention.

Each of FIGS. 17A-17K illustrates a test pattern and a competing visualstimulus which may be used as a DVS as they may appear on part of thescreen 112 of the system 105 of FIG. 1 or as may be projected on an areaof interest of a tested retina. For the sake of clarity of illustration,the fixation target is not shown in FIGS. 17A-17K, but may be any typeof suitable fixation target as disclosed and illustrated in detailhereinabove.

In the example illustrated FIG. 17A, the test pattern is a horizontalstraight line 860 and the competing visual stimulus used as a DVS is agraphic symbol 960 schematically resembling a human face.

In the example illustrated FIG. 17B, the test pattern is a horizontalsegmented straight line 862 and the competing visual stimulus used as aDVS is a triangular pattern 962.

In the example illustrated FIG. 17C, the test pattern is a horizontalstraight line 864 and the competing visual stimulus used as a DVS is arectangular pattern 964.

In the example illustrated FIG. 17D, the test pattern is a horizontalstraight line 866 and the competing visual stimulus used as a DVSincludes three dots 966A, 966B, and 966C arranged in a triangularpattern 966.

In the example illustrated FIG. 17E, the test pattern is a straighthorizontal dotted line 868 and the competing visual stimulus used as aDVS is a pattern 968 shaped as the numeral “5”.

In the example illustrated FIG. 17F, the test pattern is a verticalstraight line and the competing visual stimulus used as a DVS is apattern 970 comprising three concentric rings 970A, 970B, and 970C.

In the example illustrated FIG. 17G, the test pattern is a verticalstraight line and the competing visual stimulus used as a DVS is aslanted short line 972 which is inclined at an angle to the verticalline 872.

In the example illustrated FIG. 17H, the test pattern is a verticalstraight line 874 and the competing visual stimulus used as a DVS is anarrow-like pattern 974.

In the example illustrated FIG. 17I, the test pattern is a horizontalstraight line 876 and the competing visual stimulus used as a DVS is acircular pattern 976 which is superimposed on the line 876.

In the example illustrated FIG. 17J, the test pattern is a verticalstraight line 878 and the competing visual stimulus used as a DVScomprises a gap 978 (a missing part) in the line 878.

In the example illustrated FIG. 17K, the test pattern is a horizontalstraight line 880 and the competing visual stimulus used as a DVScomprises a part 880A of the line 880. The part 880A may have a colorwhich is different than the color of the remaining parts of the line880. Alternatively, the part 880A may have another visually perceivablecharacteristic, such as brightness, luminance, or the like, which isdifferent than the same characteristic of the remaining parts of theline 880.

In performing the tests, the test patterns may be projected at differentlocations on the tested retina, using any of the test methods disclosedhereinabove (including, but not limited to the “flash” and the “movingline” methods). The visual patterns which are being used as competingvisual stimuli or DVS may be projected on the retina before, during, orafter the presentation of the test patterns as disclosed in detailhereinabove. In different repetitions one or more characteristics orparameters of the competing visual stimulus may be varied in order tochange it's efficacy as a competing or distracting stimulus.

For example one or more characteristic of the competing stimulus may bechanged, including, but not limited to, the size, the color, thebrightness, the hue, or the distance of the DVS from the test patternmay be varied. In specific forms of competing stimuli some types ofcharacteristics may be changed. For example, for the competing stimulus966 of FIG. 17D, the distance between the dots 966A, 966B, and 966C maybe increased or decreased, but many other different types of changes maybe made to change the competing efficacy or distracting efficacy of thecompeting stimulus or DVS.

Generally, the types and spatial arrangement of the test patterns andthe competing visual stimuli, and the changing of the parameters orcharacteristics of the competing visual stimulus may be empiricallydetermined by performing suitable clinical studies to test the efficacyof various different forms of visual (or other) competing stimuli(graded or non-graded) as competing stimuli. Such tests may be performedon test subjects having normal healthy retinas, by using ADs insertedinto the test patterns and empirically assessing the competing efficacyof the competing stimuli as disclosed hereinabove. Alternatively oradditionally, the tests may be performed on patients clinicallydiagnosed to have certain stages of AMD and various degrees of retinalor choroidal lesions.

It is also noted that the different competing stimuli used within a testneed not be quantitatively graded. Turning briefly to FIG. 17C, whilechanging the size of the rectangular pattern 964 may suitably changeit's efficacy as a competing stimulus or DVS, it may also be possible touse competing stimuli having qualitative differences in the test. Forexample it may be possible to use a red rectangular competing stimulusof a first size and a yellow rectangular competing stimulus having asecond different size as competing visual stimuli within the same test,provided one pattern having a specific combination of characteristics isempirically determined to have a competing efficacy or distractingefficacy which is different than another of the used competing stimulihaving a different combination of characteristics.

It is noted that because the efficacy of different competing visualstimuli may differ significantly, it may be also possible to mixdifferent types of stimuli in the same test. For example in accordancewith one possible embodiment of the invention, it may be possible to usethe graphic symbol 960 (FIG. 17A, the rectangular pattern 964 (FIG. 17C)and the arrow-like pattern 974 (FIG. 17H) in the same test depending ontheir efficacy as competing visual stimuli or distracting stimuli. Thus,such combinations of different competing stimuli may be used to assessthe degree, or size, or severity of a retinal or choroidal lesion orabnormality, based on their empirically tested efficacy.

It is noted that many possible variations and permutations of the DVS ofthe present invention are possible which are included within the scopeof the present invention. A few non-limiting examples may include, butare not limited to, DVS which comprise one or more blinking segments ofthe test pattern, or one or more blinking portions of a continuous testpattern, or any other visual patterns or images which may or may notpartially overlap the test pattern and which may have different colorsthan the test pattern, or a gray level, or a luminosity, or brightnesswhich is different than the gray level, or the luminosity, or thebrightness of the test pattern, respectively, or any suitablecombinations of the above differences.

It will be appreciated by those skilled in the art that combinations ofthe above properties of the DVS may also be possible. For example, theDVS may include one or more segments of the test pattern which may havea different color than the color of the remaining segments of the testpatterns and may also blink (turn on and off at a desired frequency).

Thus, DVS types usable in the present invention are not limited to theexemplary embodiments described herein but may be any suitable type ofvisual stimulus which is effective in affecting the probability that thepatient will report a PROD when a test pattern is presented to thepatient at a location such that the image of the test pattern isprojected on a lesioned retinal (or choroidal) region.

By repeating the presentation of the test pattern and the DVS, varying(grading) one or more of the parameters or characteristics of the DVS,and recording the patient's responses to the presentation of the teststimuli it may be possible to analyze the competition of the DVS withthe PROD and to empirically determine classification criteria forvarious AMD stages, or for other stages of other different retinalpathologies or diseases.

The parameters of the DVS that may be varied (or graded) in differentpresentations of test patterns may be, but are not limited to, one ormore of the color (or colors) of the DVS, the brightness of the DVS (theabsolute DVS brightness or the brightness of the DVS relative to thebrightness of the test pattern), the luminosity of the DVS, the graylevel of the DVS, the frequency of blinking of the DVS, the size ordimensions or shape of the DVS, the distance of the DVS from the testpattern, the inclination of the DVS relative to the test pattern, orcombinations thereof. Additionally, it may be possible to use a group ofdifferent DVS types which are empirically selected on the basis ofhaving different psychophysical efficacy as distracting stimuli.

Another lesion grading method may be implemented, in accordance withanother embodiment of the present invention by introducing a controlleddegree of “visual noise” into the test. For example, while thebackground on which the test patterns are presented may be a uniformblack background, the background may also be a variable background. Forexample, one or more of the visual parameters the individual pixels (orof pixel groups) on the screen 112 which form the background for thetest pattern may be varied randomly, or pseudo-randomly, orperiodically, or aperiodically. The pixel parameters which may be variedmay include, but are not limited to, the intensity, color, luminosity,gray level, hue (for pixel groups or single composite pixels), and thelike.

The “visual noisiness” of the background may be varied between differentpresentations of test patterns, thus, effectively allowing gradeddegrees of visual noise which may have different efficacy in changingthe probability that the patient will report a PROD when a test patternis presented to the patient on the noisy background at a location suchthat the image of the test pattern is projected on a lesioned retinalregion.

Such graded degrees of background visual noise may be implemented, interalia, by changing the frequency of the variation of the pixel or pixelgroup parameters, by changing the range of pixel parameter valuesbetween which the pixels are allowed to vary (for example, by increasingor decreasing the range of values within which the pixels' brightness,or the pixels' color, or the pixels' gray level is allowed to vary), orby modifying the number and/or the distribution of the background pixelsthat are varied (such as, for example, by changing the percentage ofbackground pixels for which one or more visually detectable parametersare allowed to vary, or by suitably changing or modifying the values ofother suitable parameters in a way which may affect the characteristicsof the background noise).

Thus, the noisy background types usable in the present invention are notlimited to the exemplary embodiments described herein but may be anysuitable type of visual background variation or degree which iseffective in affecting the probability that the patient will report aPROD when a test pattern is presented to the patient at a location (onthe noisy background) such that the image of the test pattern isprojected on a lesioned retinal region.

By repeating the presentation of the test pattern, while varying(grading) one or more of the parameters of the background, and recordingthe patient's responses to the presentation of the test stimuli ondifferent backgrounds it may be possible to analyze the competition ofthe noisy background with the PROD and to empirically determineclassification criteria for various AMD stages, or for other stages ofother different retinal pathologies or diseases.

It is noted that generally it may be possible to subject the testedindividual to a competing sensory stimulus (of any experimentallyeffective sensory modality) before, or during, or after the presentationof the test pattern to the tested individual, or before and during thepresentation of the test pattern to the tested individual, or during andafter the presentation of the test pattern to the tested individual, orbefore and during and after the presentation of the test pattern to thetested individual. The selection of the timing and duration of thepresentation of the CS may be determined, inter alia, by the type andsensory modality of the CS, the method of presentation of the testpattern, the type and duration of the test patterns, and other practicalconsiderations. It will be appreciated that the specific timing andduration parameters of the competing auditory stimuli of EXPERIMENT 3and EXPERIMENT 4 above are given by way of example only and many othervariations of the timing and duration of the auditory competing stimulusor of any other types of auditory, or visual competing stimuli or othersensory modality of competing sensory stimuli may be used in variousimplementations of the method of the present invention.

It is noted that while the experiments disclosed herein demonstrate theuse of competing stimuli having graded stimulus parameter(s), theinvention is not limited to the use of competing stimuli which aregraded. The experiments with auditory competing stimuli disclosed hereindemonstrate that while grading the sound intensity may be used to varythe competing efficacy of the CS, other non-graded changes in thestimulus may be effectively used to vary the competing efficacy of theCS (such as, but not limited to differences the spectral content of thesound). Moreover, in accordance with yet another embodiment of thepresent invention, it may be possible to used competing stimuli havingdifferent sensory modalities in the same test.

For example, it may be possible to perform the testing of the presentinvention by using within the same test visual competing stimuli andauditory competing stimuli. In a non limiting example, the system 305 ofFIG. 15 may be used to deliver auditory competing stimuli (as disclosedin detail hereinabove to the tested individual 100 together with some ofthe repetitions of the displaying of the test patterns (such as, but notlimited to, the segmented straight line test patterns disclosedhereinabove and illustrated in FIGS. 3, 5B, and 5E) while in some otherrepetitions of the displaying of the test patterns of the same test, thetest patterns may include visual competing stimuli, such as, but notlimited to, artificial distortions (such as for example any of theartificial distortions shown in FIG. 5J, or partially shown in FIG. 6,or the like) or, alternatively, the test patterns may be presentedtogether with other competing visual stimuli (such as but not limitedto, any of the DVS or competing visual stimuli disclosed herein andillustrated in the examples of FIGS. 17A-17K, or the like). Since eachof the different competing stimuli (including but not limited to, anytype of AD or DVS and auditory competing used within the same test) mayhave a different competing efficacy, it is possible to empiricallydetermine the specific efficacies of such competing stimuli inexperiments in known clinically diagnosed patient groups and toestablish suitable diagnostic criteria for use in screening or testingpatients as disclosed in detail hereinabove for experiments using gradedartificial distortions only.

In an exemplary mixed modality test one may use two repetitions of apresentation of a straight segmented line together with exposing thetested individual to sound type 2 (as disclosed in detail in EXPERIMENT4 above) and two repetition of presenting an artificially distorted testpattern (such as, but not limited to, the artificial distortion having aheight of 0.19° of EXPERIMENT 1 above) at each tested retinal location.When using competing stimuli of different sensory modalities within thesame test, the criteria for establishing the clinical stage of AMD (orof other types of eye disease) by empirically determining the diagnosticcriteria in experiments using known clinically diagnosed patient groups,as disclosed in detail hereinabove in EXPERIMENT 1.

The determination of suitable diagnostic criteria (for assessing theclinical stage of AMD in patients or for determining the stages of othertypes of eye disease) using single sensory modality competing stimuli ormixed sensory modality competing stimuli within the same test may beimplemented by those skilled in the art based on the specific examplesin the experiments disclosed and the general principles and methods ofcompetition of stimuli as disclosed herein.

It is further noted that the methods, systems and devices of the presentinvention may be used to detect and assess retinal and choroidal lesionswhich cause vision abnormalities in the eye. While the devices methodsand systems disclosed hereinabove and illustrated in the drawings havebeen adapted for detecting and assessing the presence and/or clinicalstages of AMD, the devices methods and systems disclosed may also beused or adapted for detecting or assessing other types of visionabnormalities or eye diseases. For example the following types of eyediseases or retinal or choroidal pathologies may be detected or assessedor diagnosed by suitable adaptation and/or modifications of the methodsdevices and systems of the present invention, ocular hystoplasmosis,myopia, central serous retinopathy, central serous choroidopathy,glaucoma, diabetic retinopathy, media opacities (such as, but notlimited to, cataract), retinitis pigmentosa, optic neuritis, epiretinalmembrane, vascular abnormalities and/or occlusions, choroidaldystrophies, retinal dystrophies, macular hole, choroidal or retinaldegeneration, lens abnormalities, and the like.

It will be appreciated that the preferred embodiments disclosedhereinabove and illustrated in the drawings are given by way of exampleonly and that many variations, permutations and modifications of thepresent invention may be made which are within the scope and spirit ofthe present invention.

1-72. (canceled)
 73. A method for obtaining data on the vision of anindividual, comprising: presenting, for a first duration, a test patternto the individual, to allow the individual to form a perceived image ofsaid test pattern; receiving from said individual, input indicative of adifference between said perceived image and the test pattern, if saidindividual perceived difference, the presenting and receiving beingrepeated one or more times, wherein for at least one of the repetitions,said individual is subjected to a competing sensory stimulus; andanalyzing the received input to determine information on the vision ofsaid individual, wherein the analysis is at least partially responsiveto one or more characteristics of said competing sensory stimulus.74-143. (canceled)
 144. A method according to claim 73, wherein saidfirst duration is in the range of 100-160 milliseconds.
 145. A methodaccording to claim 73, wherein analyzing the received input comprisesanalyzing to determine whether the individual has an eye disease.
 146. Amethod according to claim 73, wherein analyzing the received inputcomprises determining if said individual belongs to a group having adefined clinical stage of an eye disease.
 147. A method according toclaim 73, wherein said eye disease is selected from the group consistingof age-related macular degeneration, choroidal neovascularization,ocular histoplasmosis, myopia, central serous retinopathy, centralserous choroidopathy, glaucoma, diabetic retinopathy, media opacities,cataract, retinitis pigmentosa, optic neuritis, epiretinal membrane,vascular abnormalities, vascular occlusions, choroidal dystrophies,retinal dystrophies, macular hole, choroidal degeneration, retinaldegeneration, lens abnormalities, and combinations thereof.
 148. Amethod according to claim 73, wherein the analysis is at least partiallyresponsive to the magnitude of the competing sensory stimulus.
 149. Amethod according to claim 73, wherein the analysis is at least partiallyresponsive to the position and/or orientation of the test pattern. 150.A method according to claim 73, wherein the analysis is at leastpartially responsive to patient indications of locations within thepatterns of the differences between the perceived image and the testpattern.
 151. A method according to claim 73, wherein the competingstimulus in at least one of the repetitions is presented only before thepresenting of the test pattern.
 152. A method according to claim 73,wherein the competing stimulus in at least one of the repetitions ispresented only during at least part of the first duration.
 153. A methodaccording to claim 73, wherein the competing stimulus in at least one ofthe repetitions is presented after at least part of the first duration.154. A method according to claim 73, wherein the individual is subjectedto the competing sensory stimulus during a period substantiallycoinciding with the first duration.
 155. A method according to claim 73,wherein at least one of the competing stimuli comprises a stimulus thatchanges over the time in which the individual is subjected to thestimulus.
 156. A method according to claim 73, wherein the competingstimulus comprises an auditory stimulus.
 157. A method according toclaim 73, wherein the competing stimulus comprises a visual stimulus.158. A method according to claim 73, wherein the competing stimuluscomprises a tactile stimulus.
 159. A method according to claim 73,wherein the competing stimulus comprises a nociceptive or asomatosensory stimulus.
 160. A method according to claim 73, wherein thecompeting stimulus is not a distortion of the test pattern.
 161. Amethod according to claim 73, wherein the competing stimulus isdifferent for at least some of the repetitions.
 162. A method accordingto claim 161, wherein the competing stimulus of different repetitionshas different durations or different beginning times relative to thefirst duration.
 163. A method according to claim 161, wherein thecompeting stimulus of different repetitions has a different magnitude.164. A method according to claim 161, wherein the competing stimulus ofdifferent repetitions has a different shape, pattern, color, orintensity.
 165. A method according to claim 73, wherein said competingstimulus is not a part of the test pattern.
 166. A method according toclaim 73, wherein said competing stimulus is a noisy visual backgroundof the test pattern.
 167. A method according to claim 73, wherein saidcompeting stimulus is within the test pattern.
 168. A method accordingto claim 167, wherein said competing stimulus comprises an artificialdistortion which mimics the appearance of a distortion perceived by anindividual when the test pattern is presented at a location of theretina of the individual which comprises an abnormality.
 169. A methodaccording to claim 167, wherein at least one of the inputs of theindividual are analyzed to determine a probability that the input is dueto the competing stimulus.
 170. A method according to claim 167, whereinthe indications are given a weight for use in the analysis responsive toa distance between the indications and the competing stimulus.
 171. Amethod according to claim 73, comprising fixating the individual'svision at or about a fixation target before presenting the test pattern.172. A method according to claim 73, wherein receiving input indicativeof a difference between the perceived image and the test patterncomprises receiving input on a temporary distortion of the test pattern.173. A method according to claim 73, wherein receiving input indicativeof a difference between the perceived image and the test patterncomprises receiving input on perceived relative motion in the testpattern.
 174. A method according to claim 73, wherein receiving inputindicative of a difference between the perceived image and the testpattern comprises receiving input on a misaligned segment in theperceived image of the test pattern.
 175. A method according to claim73, wherein receiving input indicative of a difference between theperceived image and the test pattern comprises receiving input on ablurring of the perceived image relative to the test pattern.
 176. Amethod according to claim 73, wherein the test pattern is presented atdifferent locations in at least some of the repetitions.
 177. A methodaccording to claim 176, wherein the different locations of the testpattern map a selected region of a patient's retina at a desiredresolution.
 178. A method according to claim 73, wherein the testpattern is presented with different orientations in at least some of therepetitions.
 179. A method according to claim 73, wherein said testpattern is a straight line or a segmented straight line.
 180. A methodaccording to claim 73, wherein presenting the test pattern comprisesdisplaying on a display device or projecting with a beam scanningdevice.
 181. A method for obtaining data on an eye in an individual,comprising: presenting for a first duration a test pattern to theindividual, to allow the individual to form a perceived image of saidtest pattern; receiving from said individual, input indicative of adifference between said perceived image and the test pattern, if saidindividual perceived a difference; and the presenting and receivingbeing repeated one or more times, wherein for at least one of therepetitions said individual is subjected to a predetermined visualcompeting sensory stimulus, within the test pattern; and analyzing thereceived input to determine information on an eye of said individual.182. A method according to claim 181, wherein the competing stimulus ofdifferent repetitions have different magnitudes.
 183. A method accordingto claim 182, wherein the analysis is at least partially responsive tothe magnitude of the competing sensory stimulus.
 184. A method accordingto claim 181, wherein said first duration is in the range of 100-160milliseconds.
 185. Apparatus for eye analysis, comprising: a patternpresenting unit; an input device operative to receive input from anindividual; and a processing unit adapted to generate one or morepatterns to be presented sequentially to the individual through thepattern presenting unit, to generate a competing stimulus to which theindividual is subjected with relation to at least one of the testpatterns, to receive, through the input device, input indicationsrepresenting, for at least one of the test patterns, a differenceobserved by said individual between a perceived image of the testpattern and the test pattern, and to analyze the received inputindications to determine information on the vision of the individual.186. Apparatus according to claim 185, wherein the processing unit isadapted to analyze the input indications at least partially responsiveto one or more characteristics of the competing stimulus correspondingto one or more of the test patterns.
 187. Apparatus according to claim186, wherein the processing unit is adapted to analyze the inputindications at least partially responsive to a magnitude of thecompeting stimulus corresponding to one or more of the test patterns.188. Apparatus according to claim 185, wherein the processing unit isadapted to generate for each of a plurality of the presented patterns, acompeting stimulus with a magnitude level, the magnitude levels of atleast two of the competing stimulus being different from each other.189. Apparatus according to claim 185, wherein the processing unit isadapted to provide an indication on whether the individual has an eyedisease.
 190. Apparatus according to claim 185, wherein the processingunit is adapted to provide an indication on whether the individualbelongs to a group having a defined clinical stage of an eye disease.191. Apparatus according to claim 185, wherein processing unit isadapted to receive indications of locations within the patterns of thedifferences between the perceived image and the test pattern. 192.Apparatus according to claim 185, wherein the generated competingstimuli are presented to the patient through the pattern presentingunit.
 193. Apparatus according to claim 192, wherein the processing unitis adapted to assign the input indications weights responsive to adistance between the indications and the competing stimuli. 194.Apparatus according to claim 192, wherein at least one of the competingsensory stimuli comprises a blurring of a segment of the test pattern.195. Apparatus according to claim 192, wherein at least one of thecompeting sensory stimuli comprises a change in the shape of the testpattern.
 196. Apparatus according to claim 185, comprising a speaker andwherein the competing stimuli are provided to the individual through thespeaker.
 197. Apparatus according to claim 185, wherein the competingstimulus with relation to at least one of the test patterns is providedto the individual at least partially before or after the test pattern ispresented.
 198. Apparatus according to claim 185, wherein the processingunit analyzes at least one of the inputs of the individual to determinea probability that the input is due to a competing stimulus. 199.Apparatus according to claim 185, wherein the processing unit is adaptedto generate at least some of the one or more patterns to be presentedsequentially, in different locations on the eye of the individual. 200.Apparatus according to claim 185, comprising a competing stimuligenerating unit adapted to provide the individual with tactile stimuli.201. Apparatus according to claim 185, wherein the pattern presentingunit comprises a display device or a beam scanning device.